Advertisement

Complications and Toxicities Associated with Cancer Therapies in the Intensive Care Unit

  • Melvin J. Rivera
  • Bryan Do
  • Jeffrey C. Bryan
  • Terri Lynn Shigle
  • Rina PatelEmail author
Living reference work entry
  • 111 Downloads

Abstract

Advances in the management of hematologic malignancies and solid tumors have given rise to diverse modalities to treat cancer other than cytotoxic chemotherapy, including targeted therapies, immunotherapies, and cellular therapies. Currently, there are over 175 FDA-approved antineoplastic agents in the United States, many with a diverse and profound toxicity profile. Complications of antineoplastic therapy may result in the need for intensive care unit (ICU) admission to provide acute symptom management. Accordingly, ICU providers caring for cancer patients should have a working knowledge of the toxicities and complications associated with antineoplastic therapy.

Keywords

Chemotherapy Immunotherapy Cancer Toxicity Oncology Critical care Intensive care Complications Adverse effects Antineoplastic agents 

Introduction

The prevalence of cancer has grown tremendously and with that so has the need for new or repurposed anticancer therapies. Advances in the management of hematologic malignancies and solid tumors have given rise to diverse modalities to treat cancer other than cytotoxic chemotherapy, including targeted therapies, immunotherapies, and cellular therapies. There are over 175 approved antineoplastic agents in the United States and more in development with unique toxicity profiles [163]. This has created a unique opportunity for critical care specialists to manage complications of critically ill cancer patients receiving anticancer therapies.

Toxicities of Anticancer Therapy

Tables 1A–H provides a list of antineoplastic agents and toxicities that may necessitate a higher level of care and/or impact care within the intensive care unit (ICU). These tables are not all-inclusive of every minor adverse effect of each agent. Instead, they focus on toxicities that are considered severe/life-threatening complications or clinically relevant (e.g., grade 3 or 4 adverse effects). Agents that did not meet the criteria for addition to Tables 1A–H include the following: azacitidine, cladarabine, decitabine, elotuzumab, hydroxyurea, ixazomib, lomustine, olaratumab, omacetaxine, procarbazine, talimogene, valrubicin, and venetoclax.

Table 1A

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

5-Fluorouracil (5-FU)

X

X

X

 

X

    

X

                    

X

See Note 1

Abemaciclib

   

X

                

X

          

See Note 2

Acalabrutinib

    

X

X

                     

X

X

  

See Note 3

Ado-trastuzumab

X

 

X

     

X

           

X

       

X

  

See Note 4

Afatinib

  

X

     

X

      

X

    

X

         

X

See Note 5

Aflibercept

X

  

X

   

X

       

X

 

X

          

X

  

See Note 6

Aldesleukin

X

   

X

    

X

     

X

    

X

   

X

      

See Note 7

Alectinib

    

X

   

X

      

X

    

X

  

X

       

See Note 8

Alemtuzumab

                           

X

   

See Note 9

1Cases of hyperammonemic encephalopathy have occurred within 72 h of infusion initiation. Most cases of hyperammonemic encephalopathy are treated with ammonia lowering therapies. Cases of acute cerebellar syndrome have also been reported. Higher incidence of cardiac toxicity with infusion vs bolus dosing of 5FU [60, 149, 151, 238]

2Delayed hepatotoxicity (ALT and AST elevations of grade 3 or greater) with median onset 2–6 months, generally resolving to less than grade 3 in 2 weeks with dose interruption, reduction, discontinuation, or delay [137, 225]

3Atrial fibrillation and flutter can occur. PJP prophylaxis and CMV monitoring are recommended. Major hemorrhage has been reported with BTK inhibitors. Consider withholding 3–7 days prior to procedures depending on risk of bleeding [13, 41]

4GI, CNS, and pulmonary bleeding have occurred in trials with some fatalities. Higher risk in patients on anticoagulants or antiplatelet therapy. Liver failure, hepatic encephalopathy, idiopathic noncirrhotic portal hypertension, and death have been reported [82]

5Hepatic impairment is rare but fatalities have been reported. Diarrhea can be severe and may lead to dehydration and subsequent renal failure [31]

6Hypertension onset is generally within the first two cycles. Proteinuria, nephrotic syndrome, and TMA have been associated with ziv-aflibercept [210]

7High-dose IL-2 has a black box warning for capillary leak syndrome, CNS toxicity, and increased risk for disseminated infection. Use should be restricted to patients with normal cardiac and pulmonary function. IL-2 should only be administered under the supervision of an experienced cancer chemotherapy physician in a facility with ICU facilities available. Consensus guidelines are available to provide criteria for safe administration and toxicity management [66, 196]

8Symptomatic bradycardia can occur. When treating hypertension use caution when administering antihypertensive agents that can cause bradycardia. Severe renal events are rare but fatal cases have been reported. The majority of hepatotoxicity occurs within the first 3 months of therapy. Monitor CPK and for signs or symptoms of muscle pain or weakness. Median time to grade 3 CPK elevations 14 days [86]

9PJP and HSV prophylaxis is recommended from initiation of treatment until 2 months following last dose or until CD4+ >200/mm3 [91]

Table 1B

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Arsenic trioxide

     

X

   

X

     

X

          

X

    

See Note 10

Asparaginase Erwinia chrysanthemi

X

  

X

               

X

X

  

X

       

See Note 11

Atezolizumab

X

 

X

     

X

     

X

X

   

X

X

X

X

X

X

    

X

X

See Note 12

Avelumab

X

     

X

 

X

     

X

X

   

X

X

X

X

X

X

     

X

See Note 13

Axicabtagene ciloleucel

X

X

X

 

X

   

X

      

X

    

X

    

X

 

X

   

See Note 14

Axitinib

X

 

X

X

   

X

      

X

  

X

  

X

  

X

X

   

X

  

See Note 15

Belinostat

     

X

                         

See Note 16

Bendamustine

                              

X

See Note 17

Bevacizumab

X

 

X

X

   

X

X

    

X

 

X

 

X

          

X

  

See Note 18

Bexarotene

                   

X

X

   

X

      

See Note 19

Bleomycin

        

X

   

X

                  

See Note 20

Blinatumomab

X

X

                 

X

X

    

X

     

See Note 21

Bortezomib

X

 

X

     

X

 

X

         

X

          

See Note 22

Bosutinib

           

X

   

X

               

See Note 23

Brentuximab vedotin

        

X

        

X

X

X

       

X

  

X

See Note 24

Brigatinib

    

X

  

X

X

          

X

   

X

       

See Note 25

Busulfan

 

X

      

X

   

X

       

X

          

See Note 26

Cabazitaxel

        

X

      

X

X

X

X

            

See Note 27

Cabozantinib

X

  

X

   

X

         

X

 

X

    

X

   

X

  

See Note 28

10Differentiation syndrome usually occurs during the first cycle of arsenic, median onset 17 days (7–24 days) and is commonly associated with the development of hyperleukocytosis, pulmonary edema, generalized edema, headache, bone pain, and renal failure. Management includes steroids and/or discontinuation of arsenic depending on severity. Although QT prolongation is well described, clinically significant arrhythmias are rare when appropriately monitored and managed – maintain serum potassium levels above 4 mEq/L and magnesium levels above 1.8 mg/dL [201, 215]

11Similar to the other asparaginase formulations, pancreatitis, abnormal transaminases, coagulation abnormalities including thrombosis and hemorrhage, and hyperglycemia can occur [115]

12May cause severe immune-mediated adverse events including pneumonitis, median onset 3 months (3 days to 18.7 months) and median duration 2–6 weeks, up to 12.6 months or longer; severe diarrhea, median onset 3–7 weeks (12 days to 3.4 months); hepatitis, median onset 1 month; hypothyroidism, median onset 5 months (15 days to 31 months); hypophysitis, rare, two case reports, onset 12–13 months. May aggravate underlying autoimmune disorders. Management includes holding therapy, systemic corticosteroids, +/− additional immunosuppressants (e.g., infliximab, mycophenolate, and vedolizumab). Consider PJP prophylaxis in patients with prolonged corticosteroid exposure [33, 89, 122, 160]

13May cause severe immune-mediated adverse events including pneumonitis, median onset 2.5 months (3 days to 11 month); hepatitis, median onset 3.2 months (7 days to 15 months); colitis, median onset 2.1 months (2 days to 11 months); adrenal insufficiency, median onset 2.5 months; immune-mediated thyroid disorders, median onset for 2.8 months (2 weeks to 13 months). May aggravate underlying autoimmune disorders. Management includes holding therapy, systemic corticosteroids, +/− additional immunosuppressants (e.g., infliximab, mycophenolate, and vedolizumab). Consider PJP prophylaxis in patients with prolonged corticosteroid exposure [33, 73]

14ICANS: Median onset 4 days (1–43 days); median duration of neurologic toxicities 17 days. Most common neurological toxicities: encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia, and anxiety. Fatal and serious cases of cerebral edema have occurred. Other serious events included leukoencephalopathy and seizures

CRS: Median onset 2 days (1–12 days); median duration 7 days (2–58 days). Key manifestations of CRS: fever, hypotension, tachycardia, hypoxia, and chills

Management of CRS depends on grading or severity but includes supportive care, interleukin-2 receptor antagonist tocilizumab, and/or systemic corticosteroids

Grade 2 or higher ICANS without CRS should be treated with supportive care and/or systemic corticosteroids as there is insufficient data with tocilizumab in this setting. Consider anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis for any grade 2 or higher neurologic toxicities

Cardiac arrhythmias (e.g., atrial fibrillation, ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, HLH/MAS can occur

Hypogammaglobulinemia secondary to B-cell aplasia may persist for up to 13 months and increase the risk for infections. PJP and HSV prophylaxis is recommended for at least 1 year after CAR-T cell therapy [128, 161, 221]

15Wound healing complications – hold for at least 24 h prior to surgery and restart when wound healed. RPLS is rare but serious. Monitor for headache, seizure, lethargy, and hypertension [187]

16QT prolongation is a class effect of HDAC inhibitors, although the incidence may be lower than initially reported. Optimize serum potassium and magnesium levels [205, 228]

17Severe cutaneous reactions including SJS, TEN, DRESS, and bullous pemphigoid have been reported [45, 131, 239]

18RPLS: onset of symptoms from 16 h to 1 year after the first dose. Monitor for headache, seizure, lethargy, and hypertension. Wound healing: if possible wait at least 4 weeks after bevacizumab discontinuation for major surgical procedures and do not restart for at least 4 weeks after surgery or until wound is fully healed. Cases of TMA have been reported. Higher incidence of GI perforation in patients with previous pelvic irradiation. Severe pulmonary hemorrhage reported in NSCLC [30, 75, 87, 107, 197, 218]

19Bexarotene induces significant lipid abnormalities, usually occurring within 2–4 weeks. Pancreatitis associated with hypertriglyceridemia has been reported. Interrupt treatment and evaluate if pancreatitis is suspected; triglycerides should be maintained <400 mg/dL utilizing HMG-CoA reductase inhibitors or fenofibrate. Gemfibrozil is not recommended due to increased bexarotene and triglyceride levels. Bexarotene rapidly suppresses TSH levels by directly inhibiting TSH secretion and thyroid hormone metabolism [98, 236]

20Bleomycin may cause pneumonitis leading to pulmonary fibrosis. Risk factors include age > 70 years, cumulative lifetime dose > 450 units, prior mantle radiation, renal impairment, oxygen exposure, smoking, and granulocyte-colony stimulating factor use [16, 37]

21Neurotoxicities include tremors, confusion, encephalopathy, aphasia, and seizures, which are reversible in most cases. Onset of symptoms usually occurs around day 7 of the first cycle of treatment. Management includes treatment with dexamethasone, with or without blinatumomab interruption, and anti-seizure medication as indicated. CRS is managed with dexamethasone, with or without blinatumomab interruption, and tocilizumab as indicated. Hepatotoxicity can present alone or in association with CRS [7, 242, 243]

22New onset or exacerbation of HF, pneumonitis, and pulmonary hypertension may occur. Acute liver failure and RPLS have been reported rarely with bortezomib. HSV/VZV prophylaxis is required during therapy due to risk of reactivation [150]

23Most common toxicities are GI (i.e., diarrhea, nausea, and vomiting). Pleural effusions may develop in patients with a prior history of pleural effusions and dasatinib exposure [125]

24Serious and fatal cases of GI complications (i.e., acute pancreatitis, hemorrhage, obstruction, perforation) and hepatotoxicity have been reported, with higher incidence in patients with GI or liver disease involvement. Cases of PML and death due to JC virus infection have occurred with median onset of 7 weeks after initiation (3–34 weeks) ([48], Seattle [217])

25Symptomatic bradycardia can occur. When treating hypertension, use caution when administering with antihypertensive agents that can cause bradycardia. Higher incidence and earlier onset of pneumonitis compared to other ALK inhibitors. ILD/pneumonitis typically occurs within 9 days of initiation – higher incidence with 180 mg/day vs 90 mg/day. Monitor CPK at baseline and periodically for signs or symptoms of muscle pain or weakness [9, 127].

26Anti-seizure prophylaxis required with administration of busulfan. VOD is a risk among patients receiving busulfan, but the incidence has decreased since the transition in standard of care from oral to IV busulfan and the use of PK for dosing. Avoid use of acetaminophen, metronidazole, or introduction of any medication that may inhibit/induce CYPA3A4 for at least 72 h before, during, and for 72 h after busulfan administration as these are major drug interactions that will affect PK dosing [52, 181]

27Case reports of hemorrhagic cystitis, which may be due to radiation recall in patients with history of pelvic irradiation. High rates of grade 3/4 neutropenia in clinical trials [97, 141, 213]

28RPLS has occurred rarely in trials. Monitor for headache, seizure, lethargy, and hypertension. Can impair wound healing – hold 28 days prior to surgery and resume once wound has healed [76]

Table 1C

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Capecitabine

X

X

X

X

X

 

X

        

X

 

X

X

 

X

         

X

See Note 29

Carboplatin

X

             

X

   

X

            

See Note 30

Carfilzomib

X

 

X

X

   

X

X

  

X

   

X

            

X

  

See Note 31

Carmustine

        

X

                      

See Note 32

Ceritinib

    

X

X

X

X

X

          

X

X

  

X

       

See Note 33

Cetuximab

        

X

                     

X

See Note 34

Chlorambucil

 

X

                            

X

See Note 35

Cisplatin

X

X

 

X

          

X

X

  

X

            

See Note 36

Clofarabine

               

X

    

X

      

X

X

X

X

See Note 37

Cobimetinib

  

X

    

X

         

X

          

X

X

 

See Note 38

Copanlisib

       

X

X

              

X

   

X

   

See Note 39

Crizotinib

    

X

X

  

X

           

X

  

X

       

See Note 40

Cyclophosphamide

  

X

 

X

 

X

 

X

     

X

 

X

   

X

          

See Note 41

Cytarabine

X

        

X

  

X

                  

See Note 42

Dabrafenib

  

X

X

 

X

  

X

              

X

    

X

  

See Note 43

Dacarbazine

                    

X

          

See Note 44

Dactinomycin

        

X

           

X

         

X

See Note 45

Daratumumab

        

X

X

                     

See Note 46

Dasatinib

    

X

X

X

 

X

 

X

X

                

X

 

X

See Note 47

Daunorubicin

  

X

                            

See Note 48

Daunorubicin and cytarabine (liposomal)

  

X

                            

See Note 49

29Cardiotoxicity: lower incidence than 5FU, mechanism thought to be due to coronary vasospasm. Higher risk in patients with cardiac or renal comorbidities. Bowel perforation: higher incidence in colon/rectal cancer but cases also reported in breast cancer patients [57, 85, 207]

30Incidence of hypersensitivity reactions increases with repeated exposure. Rate of reactions increased from 1% to 27% in women with ovarian cancer who received >7 cycles. Desensitization may require ICU admission [109, 142]

31New onset or worsening HF, restrictive cardiomyopathy, pulmonary hypertension, myocardial ischemia, and infarction, including fatalities, may occur. Patients with prior cardiovascular disease or advanced age (>75 years of age) are at an increased risk. Acute kidney injury may be associated with progressive myeloma although prerenal insults, tumor lysis-like syndrome, ATN, and TMA have occurred. Acute liver failure and RPLS have been reported rarely with carfilzomib. Monitor for headache, seizure, lethargy, and hypertension. Thromboembolism and hemorrhage risks are thought to be associated with disease-related processes or combination regimens containing immunomodulatory agents. Anticoagulation or antiplatelet therapy is not required for patients receiving carfilzomib monotherapy. HSV/VZV prophylaxis is required during therapy due to risk of reactivation [63, 178, 250]

32Black box warning for dose-related pulmonary toxicity, especially in patients receiving >1400 mg/m2 cumulative dose. Pulmonary fibrosis may have delayed onset, occurring years after treatment, especially in children. Other risk factors, aside from cumulative dose, include history of lung disease and baseline FVC or DLCO <70% [101, 253]

33Symptomatic bradycardia can occur. When treating hypertension, use caution when administering antihypertensive agents that can cause bradycardia. Cases of grade 3 and 4 pancreatitis have been reported, including fatal ones. Monitor amylase/lipase at baseline, periodically during therapy and when clinically necessary [15, 167, 227]

34Cardiopulmonary arrest and/or sudden death in 2–3% of patients with squamous cell carcinoma of the head and neck treated with cetuximab-based therapy [69]

35Patients with a history of nephrotic syndrome and receiving high pulse doses of chlorambucil are at an increased risk of seizures [195, 208]

36RPLS has been reported. Monitor for headache, seizure, lethargy, and hypertension. Renal toxicity is dose-related and becomes more prolonged and severe with repeated courses. Hypocalcemia and hypomagnesemia-related tetany have been reported. Incidence of hypersensitivity reactions increases with repeated exposure, peaking after six cycles. Desensitization may require ICU admission [38, 229]

37Older age may correlate with decreased metabolic clearance of clofarabine or possibly decreased nonrenal excretion of the drug. Clofarabine may cause a capillary leak syndrome that can be prevented and managed with steroids. Consider PJP and fungal prophylaxis. Serious and fatal hemorrhage, including cerebral, GI, and pulmonary hemorrhage have occurred [77, 186]

38Risk of GI perforation 0.3%. Median first onset of LVEF decline was 4 months (23 days to 13 months). Rhabdomyolysis: median time to first occurrence of grade 3 or 4 CPK elevations 16 days (12 days to 11 months) [84]

39PJP and noninfectious pneumonitis have been reported. PJP prophylaxis is recommended in patients with prior PJP infection or lymphopenia. Infusion-related hyperglycemia and hypertension have also occurred. Serum glucose levels typically peak at 5–8 h post infusion, whereas systolic and diastolic blood pressure peak 2 h post infusion [23]

40Symptomatic bradycardia can occur. When treating hypertension, use caution when administering with antihypertensive agents that can cause bradycardia. Pneumonitis onset is generally within 3 months of treatment initiation. Severe cases of liver injury have been reported during the first 6 weeks of therapy. Fatal cases of ketoacidosis have been reported [190, 203, 223]

41Cardiotoxicity is related to endothelial capillary damage. Risk is increased with higher doses, advanced age, prior radiation to the cardiac region, and/or prior use of other cardiotoxic agents. Reported cardiotoxicities include arrhythmias (atrial fibrillation, atrial flutter, and ventricular arrhythmias), HF, heart block, myocarditis (including hemorrhagic), pericarditis, and pericardial effusion (including cardiac tamponade). Late-onset pneumonitis (> 6 months) is associated with increased mortality. Hyperhydration plus/minus MESNA are utilized to help prevent hemorrhagic cystitis during the infusion of cyclophosphamide. VOD has been described with high doses of cyclophosphamide in combination with other agents, such as TBI or busulfan as part of a conditioning regimen for stem cell transplant [21, 62]

42Doses ≥3 g/m2 every 12 h have been reported to cause an acute cerebellar syndrome in 10–25% of patients. Patients >40 years of age who have abnormal liver or renal function, underlying neurologic dysfunction, or who receive a total dose of >30 g, are particularly vulnerable to developing cerebellar toxicity [19, 102, 118, 226]

43Median onset of cardiomyopathy is 4 months when used alone or 8 months if used concurrently with trametinib. Fever is common with dabrafenib and trametinib and can lead to hypotension, dizziness, and kidney dysfunction if dehydration occurs [171, 255]

44Hepatotoxicity may be accompanied by hepatic vein thrombosis and hepatocellular necrosis [11]

45Increased risk of VOD in children <4 years of age [182]

46Infusion-related reactions including bronchospasm, pneumonitis, and pulmonary edema may occur. Combination regimens with corticosteroids and premedication with antihistamines and antipyretics have helped alleviate symptoms, although patients may still be at risk for delayed infusion reactions. Consider bronchodilators in patients with a history of COPD or FEV1 < 80%. HSV prophylaxis should start within 1 week of initiation and continue for 3 months following treatment. May result in a false-positive Indirect Coombs test that may persist for up to 6 months after the last infusion [111]

47Optimize serum potassium and magnesium levels prior to and during therapy to reduce risk of cardiotoxicity. Pleural effusions can occur. Management of pleural effusions consists of temporary dose interruption, dose reductions, diuretics, and/or corticosteroids. Pulmonary arterial hypertension typically occurs after 8–48 months of exposure. Increased risk of bleeding in those with advanced disease and thrombocytopenia [28, 39, 55, 134, 152, 194, 220]

48Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. The incidence of cardiac toxicity increases after a total cumulative dose exceeding 400–550 mg/m2 in adults, 300 mg/m2 in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age [27]

49Cardiotoxicity may occur due to the anthracycline component (daunorubicin) of the formulation. Observe the same risk factors for cardiotoxicity as with conventional anthracyclines. This formulation is not interchangeable with other formulations of daunorubicin and cytarabine [114, 132]

Table 1D

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Dinutuximab

X

             

X

X

    

X

  

X

    

X

  

See Note 50

Docetaxel

 

X

X

     

X

X

 

X

     

X

X

 

X

         

X

See Note 51

Doxorubicin

  

X

     

X

   

X

                  

See Note 52

Doxorubicin liposomal

  

X

     

X

   

X

                  

See Note 53

Durvalumab

  

X

     

X

     

X

X

   

X

X

X

X

X

X

    

X

 

See Note 54

Enasidenib

                          

X

    

See Note 55

Epirubicin

  

X

                            

See Note 56

Erlotinib

   

X

    

X

      

X

 

X

  

X

         

X

See Note 57

Etoposide

X

X

      

X

                     

X

See Note 58

Everolimus

X

     

X

 

X

  

X

 

X

 

X

       

X

   

X

   

See Note 59

Fludarabine

X

X

      

X

                  

X

   

See Note 60

Gefitinib

        

X

        

X

  

X

         

X

See Note 61

Gemcitabine

X

       

X

X

   

X

 

X

    

X

         

X

See Note 62

Gemtuzumab ozogamicin

     

X

              

X

       

X

  

See Note 63

Ibritumomab

                              

X

See Note 64

Ibrutinib

    

X

X

                     

X

X

  

See Note 65

Idarubicin

  

X

                            

See Note 66

Idelalisib

        

X

   

X

    

X

  

X

      

X

  

X

See Note 67

50Can cause capillary leak syndrome with hypotension, severe hypokalemia and hyponatremia, HUS, and subsequent renal failure. RPLS can occur – monitor for headache, seizure, lethargy, and hypertension [245]

51Fluid retention, due to capillary leakage, can lead to non-cardiogenic pulmonary edema or pleural effusions. Diuretics recommended for treatment [162, 199, 212]

52Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. Risk of cardiomyopathy is proportional to the cumulative exposure with incidences from 1% to 20% for cumulative doses of 300 mg/m2–500 mg/m2. At a cumulative dose of 400 mg/m2, the risk of developing HF is 5% [26, 258]

53Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. Risk of cardiac toxicity has been reported to be 11% with cumulative doses between 450 and 550 mg/m2 [113]

54May cause severe immune-mediated adverse events including pneumonitis, median onset 1.8 months; hepatitis, median onset ~52 days (2–45 weeks); and immune-mediated thyroid disorders, median onset 3 months (range: 2 weeks to 13 months). May aggravate underlying autoimmune disorders. Management includes holding therapy, systemic corticosteroids, +/− additional immunosuppressants (e.g., infliximab, mycophenolate and vedolizumab). Consider PJP prophylaxis in patients with prolonged corticosteroid exposure [12, 33]

55Differentiation syndrome is commonly associated with the development of hyperleukocytosis, pulmonary edema, generalized edema, headache, bone pain, and renal failure, with a median onset of 48 days (10–340 days). Management includes steroids and/or discontinuation of enasidenib depending on severity. For management, please refer to the package insert. Patients with leukocytosis can be managed with hydroxyurea [230]

56Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. Risk of cardiomyopathy is proportional to the cumulative exposure with incidences from 0.9% to 3.3% for cumulative doses from 550 mg/m2–900 mg/m2 [144]

57The risk of CVA is increased in patients with pancreatic cancer, with a higher incidence found in those receiving erlotinib + gemcitabine (2.5%) versus gemcitabine alone. Median onset of ILD symptoms is 39 days (5 days to more than 9 months) after initiating therapy. Renal failure may arise from exacerbation of underlying baseline hepatic impairment or severe dehydration. Rare incidence of renal failure in monotherapy (0.5%) and 1.4% when combined with gemcitabine [79, 180]

58[2, 202]

59Noninfectious pneumonitis, PJP, and invasive fungal and viral infections have been reported. Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required [120, 164]

60Incidence of pulmonary toxicity 8.6%, more likely with CLL. Pneumonitis occurs days to weeks after therapy and may occur following the first cycle; management includes systemic corticosteroids. Fludarabine can also cause autoimmune hemolytic anemia (AIHA). Serious and sometimes fatal infections including opportunistic and reactivation of latent viral infections such as VZV, EBV, and JC virus have been reported [100, 231, 246]

61Median onset of ILD symptoms 3–6 weeks, with fatalities reported. Serum hepatic enzyme elevations typically occur after 4–12 weeks of treatment with a hepatocellular pattern [17]

62Associated with a range of pulmonary toxicities: interstitial pneumonitis, capillary leak, non-cardiogenic pulmonary edema, and pulmonary fibrosis; onset can be up to 2 weeks following the last dose. Potential for radiation recall. HUS has been reported, including fatalities or need for dialysis due to renal failure. Capillary leak syndrome and RPLS have been reported [46, 72, 206, 244]

63Optimize potassium and magnesium prior to and during therapy to reduce risk of cardiotoxicity. Increased risk for VOD. Median onset of hyperbilirubinemia and increases in AST and ALT 8 days and median duration 20 days following initiation of therapy [145, 224, 249]

64SJS may occur within days to 4 months following infusion [117]

65Arrhythmias (i.e., ventricular arrhythmias, atrial fibrillation, and flutter) have occurred, particularly in patients with cardiac risk factors, hypertension, acute infections, or history of arrhythmias. Cases of PJP have been reported with a median onset of 6 months (2–24 months). Invasive fungal infections (i.e., aspergillosis, cryptococcal, and mucor) have been reported. Consider PJP and fungal prophylaxis in patients with lymphopenia or prolonged corticosteroid exposure. Major hemorrhage (grade 3–4) has been reported with BTK inhibitors. Consider withholding for 3–7 days prior to procedures depending on the risk of bleeding [3, 20, 146, 176, 193, 219]

66Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. Estimated incidence of heart failure is 5–18% with doses >90 mg/m2 [258]

67Pneumonitis and organizing pneumonia may occur 1-15 months after initiation of idelalisib and should be managed with corticosteroids. GI perforation typically preceded by moderate to severe diarrhea. Median onset of diarrhea 1.9 months (range, 0.0–29.8 months). Anti-motility drugs such as loperamide are not useful in the management of idelalisib-induced diarrhea, which is best managed with dose interruptions; the median time to resolution of diarrhea can be up to 1 month. Enteric budesonide or systemic corticosteroids may be considered for treatment of severe or unresolved diarrhea, leading to shorter time to resolution compared to interruption alone (1–2 weeks vs. 1 month). Elevations in ALT or AST >5 times ULN have been observed, usually occurring within the first 12 weeks of treatment. Most transaminase elevations were reversible with dose interruption. Median time to PJP event 4.5 months after initiation. Consider PJP prophylaxis and CMV monitoring [93]

Table 1E

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Ifosfamide

X

X

X

 

X

  

X

      

X

X

X

   

X

          

See Note 68

Imatinib

  

X

        

X

     

X

  

X

       

X

 

X

See Note 69

Inotuzumab ozogamicin

                    

X

          

See Note 70

Ipilimumab

X

 

X

     

X

   

X

  

X

 

X

 

X

X

X

X

 

X

     

X

See Note 71

Irinotecan

   

X

    

X

  

X

   

X

 

X

             

See Note 72

Ixabepilone

  

X

                 

X

          

See Note 73

L-Asparaginase

X

  

X

               

X

X

  

X

       

See Note 74

Lapatinib

  

X

  

X

 

X

X

           

X

         

X

See Note 75

Lenalidomide

   

X

    

X

           

X

   

X

     

X

See Note 76

Lenvatinib

X

 

X

X

 

X

 

X

       

X

 

X

 

X

X

   

X

   

X

  

See Note 77

Lisocabtagene maraleucel

X

X

X

 

X

   

X

      

X

    

X

    

X

 

X

   

See Note 78

Mechlorethamine

                           

X

   

See Note 79

Melphalan

        

X

     

X

     

X

          

See Note 80

Methotrexate

X

       

X

   

X

  

X

 

X

  

X

      

X

  

X

See Note 81

Midostaurin

        

X

              

X

       

See Note 82

Mitomycin-C

        

X

      

X

               

See Note 83

Mitoxantrone

        

X

                      

See Note 84

Nab-paclitaxel

   

X

    

X

                      

See Note 85

Necitumumab

  

X

X

                           

See Note 86

Nelarabine

X

X

                             

See Note 87

68Ifosfamide encephalopathy (ranging from mild somnolence to confusion and hallucinations to coma) may occur within hours to days after a dose. Risk factors for CNS toxicity include hypoalbuminemia, pre-existing renal dysfunction, concomitant use of aprepitant, and prior cisplatin exposure. IV albumin and thiamine supplementation are recommended for prevention. Encephalopathy typically resolves within 2–3 days after discontinuation; however, IV methylene blue may be considered as a treatment option. Cardiotoxicity including arrhythmias (i.e., SVT, atrial fibrillation, and pulseless ventricular tachycardia), heart failure with congestion and hypotension, pericardial effusion, fibrinous pericarditis, and epicardial fibrosis may occur. VOD has been reported in combination regimens [22, 183]

69Heart failure has been reported, although mostly in those with other comorbidities and risk factors, including advanced age and previous cardiac disease. Although rare, it is worth noting the reports of interstitial pneumonia. Median onset 7 weeks (1.5–40 weeks) and presentation includes low-grade fever, dry cough, and progressive dyspnea on exertion, with or without hypoxia. Management includes steroids and/or drug discontinuation of imatinib [175]

70VOD can occur during or after treatment. Median onset of VOD was 15 days (range, 3–57 days) for patients receiving stem cell transplant [123, 124]

71Pneumonitis: highest incidence when given with nivolumab (5–10% incidence) with median onset of symptoms 2.6 months following therapy initiation. Onset of GI symptoms is typically 6 weeks or more after initiating therapy. Moderate to severe endocrine disorders: median onset 2.2–2.5 months. Immune-mediated hepatitis (grade 3 or 4): median onset 2 months. Treat toxicities by holding ipilimumab and administering corticosteroids. Consider PJP and fungal prophylaxis in patients with prolonged corticosteroid exposure. Although rare, lethal myocarditis accompanied by myositis in patients treated with a combination of nivolumab and ipilimumab has been reported [34, 40, 42]

72Pulmonary toxicity more common with irinotecan than topotecan. Higher risk in patients with pre-existing lung disease, prior thoracic radiation, use of pneumotoxic drugs, and colony-stimulating factors. Severe/fatal diarrhea can occur with irinotecan. Early diarrhea (within 24 hrs) is accompanied by anticholinergic symptoms. Late diarrhea can occur more than 24 hrs following dose administration. Cases of megacolon and bowel perforation have been reported [192]

73MI and ventricular dysfunction have been reported [35]

74Noted complications typically occur after several weeks of treatment and often during the induction phase. Encephalopathy may be related to hyperammonemia and RPLS. Serious thrombotic events, including sagittal sinus thrombosis, have been reported [5, 78, 99, 126]

75Decreases in LVEF have been reported, usually within the first 3 months of treatment. Optimize serum potassium and magnesium levels prior to and during therapy. Case reports describe serious or fatal hepatotoxicity, usually 1–3 months following treatment initiation [165, 184, 185]

76Thromboprophylaxis with either aspirin or a LMWH should be considered for patients receiving lenalidomide in combination with chemotherapy and/or dexamethasone [140, 241]

77RPLS has been reported. Monitor for headache, seizure, lethargy, and hypertension. Median time to onset of new or worsening hypertension is 16–35 days. Can impair wound healing; should be held at least 6 days prior to surgical procedures [67]

78Lisocabtagene maraleucel is a CAR T-cell therapy undergoing FDA approval. Latest available data revealed a 1% incidence of severe CRS (35% any grade CRS) and 12% incidence of severe ICANS (19% any grade ICANS). Management of CRS and/or ICANS is grading dependent but may include supportive care, tocilizumab, and/or systemic corticosteroids. Anti-seizure, PJP, and HSV prophylaxis similar to other CAR T-cell therapies should be considered [119]

79PJP and CMV pneumonia have occurred due to severe and prolonged neutropenia. Consider PJP prophylaxis and CMV monitoring [43]

80GI toxicity, including grade 3/4 mucositis, has been reported with high-dose melphalan. Cryotherapy may help prevent/reduce mucositis severity [95]

81Glucarpidase may be considered for patients receiving high-dose methotrexate (HDMTX) with delayed clearance (serum methotrexate levels > 1 μmol/L beyond 42 h after the start of HDMTX infusion) and renal dysfunction (serum creatinine >1.3 mg/dL or > 50% increase from baseline). Leucovorin calcium should not be administered within 2 h of glucarpidase due to competing binding sites. Intrathecal methotrexate is commonly associated with aseptic meningitis characterized by fever, headache, and vomiting that can last several days. Generalized and focal seizures have been reported. Methotrexate may increase the risk of developing life-threatening opportunistic infections. Do not initiate penicillins, fluoroquinolones, sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors until methotrexate has cleared [80, 129]

82Fatal events involving pulmonary toxicity have occurred [232]

83Infrequent but severe pulmonary toxicity (e.g., ARDS) has been reported. HUS and subsequent renal failure have been reported. Dose-related pulmonary toxicity (>20 mg/m2) [138, 177, 234, 248]

84Onset of cardiotoxic effects of anthracyclines can occur during or immediately after infusion (acute onset), within 1 year of exposure (early onset), and from 1–20 years (late onset) after initial exposure. Factors increasing the risk of cardiac toxicity include the extent of anthracycline exposure, higher doses, older age, pre-existing cardiac disease, concurrent or previous mediastinal radiation therapy, and concomitant administration of cardiotoxic chemotherapy regimens such as paclitaxel or trastuzumab. Estimated risk of CHF is 2.6% for doses up to 140 mg/m2 [74]

85[1]

86Cardiopulmonary arrest and/or sudden death has been reported in patients treated with necitumumab in combination with gemcitabine and cisplatin. Severe hypomagnesemia is common in those treated with necitumumab, gemcitabine, and cisplatin, with a median onset of 6 weeks. Optimize serum potassium, magnesium, and calcium during and for at least 8 weeks following administration. Cerebral stroke and MI have also been reported [68, 240]

87Most neurologic toxicities occur within 12 days of infusion or after successive cycles of therapy. The most common grade 3/4 neurologic adverse events reported include confusion, malaise, somnolence, ataxia, muscle weakness, and peripheral neuropathies [121, 130]

Table 1F

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Nilotinib

     

X

X

  

X

 

X

       

X

X

  

X

    

X

 

X

See Note 88

Niraparib

       

X

                       

See Note 89

Nivolumab

X

       

X

     

X

X

   

X

X

X

X

X

X

    

X

X

See Note 90

Obinutuzumab

                           

X

  

X

See Note 91

Ofatumumab

                           

X

  

X

See Note 92

Olaparib

   

X

    

X

  

X

                   

See Note 93

Osimertinib

  

X

  

X

  

X

                      

See Note 94

Oxaliplatin

X

X

  

X

X

  

X

   

X

X

      

X

        

X

 

See Note 95

Paclitaxel

 

X

      

X

                     

X

See Note 96

Palbociclib

   

X

                           

See Note 97

Panitumumab

   

X

    

X

                     

X

See Note 98

Panobinostat

    

X

X

                         

See Note 99

Pazopanib

X

 

X

X

 

X

 

X

X

        

X

  

X

   

X

   

X

 

X

See Note 100

PEG-asparaginase

X

  

X

               

X

X

  

X

       

See Note 101

Pembrolizumab

X

       

X

   

X

 

X

X

   

X

X

X

X

X

X

     

X

See Note 102

Pemetrexed

        

X

      

X

              

X

See Note 103

Pentostatin

               

X

    

X

      

X

   

See Note 104

Pertuzumab

  

X

    

X

                       

See Note 105

Pomalidomide

   

X

    

X

           

X

   

X

     

X

See Note 106

Ponatinib

  

X

X

X

X

X

X

           

X

X

       

X

  

See Note 107

Pralatrexate

                    

X

         

X

See Note 108

88Risk of QT prolongation warrants a baseline 12-lead EKG with repeat assessment after 7 days of therapy, following any dose change, and regularly during treatment. Optimize serum potassium and magnesium levels prior to and during therapy. Biochemical abnormalities are common (i.e., increased lipase, glucose, total bilirubin, ALT) [4, 94, 103, 135, 172, 198]

89Hypertensive crisis has been reported [237]

90May cause severe immune-mediated adverse events including pneumonitis, median onset 1.6–3.5 months (1 day to 22.3 months); nephritis, 2.7–4.6 months (9 days to 12.3 months); hepatitis, 2.1–3.3 months (6 days to 11 months); colitis, 1.6–5.3 months (2 days to 21 months); adrenal insufficiency (across several clinical trials), 3–4.3 months (15 days to 21 months); hyperthyroidism, 23 days to 1.5 months (1 day to 14.2 months); hypothyroidism, 2–3 months (1 day to 16.6 months); and hypophysitis, 4.9 months (1.4–11 months). May aggravate underlying autoimmune disorders. Management includes holding therapy, systemic corticosteroids, and +/− additional immunosuppressants (e.g., infliximab, mycophenolate, and vedolizumab). Consider PJP prophylaxis in patients with prolonged corticosteroid exposure. Although rare, lethal myocarditis accompanied by myositis in patients treated with a combination of nivolumab and ipilimumab has been reported [33, 36, 116, 133, 159, 160]

91HBV reactivation may occur during and up to 24 months after discontinuation of anti-CD20 antibodies. Patients on antiviral prophylaxis should continue for 6–12 months after completing treatment. JC virus infection resulting in PML has been reported [32, 106]

92HBV reactivation may occur during and up to 24 months after discontinuation of anti-CD20 antibodies. Patients on antiviral prophylaxis should continue for 6–12 months after completing treatment. Fatal cases of PML have been reported [32, 106]

93[14, 64]

94[18]

95Ventricular arrhythmias, including fatal Torsades de Pointes, have been reported. Optimize potassium and magnesium prior to and during therapy. Cases of pulmonary fibrosis, including fatal events, have been reported. RPLS has been reported. Monitor for headache, seizure, lethargy, and hypertension [154, 204, 211, 222]

96[29, 162]

97[191]

98Monitor for hypomagnesemia and hypocalcemia prior to, during and up to 8 weeks after therapy. Severe dermatologic complications may effect up to 15% of patients and can lead to life-threatening infectious complications such as necrotizing fasciitis and abscesses [8, 179]

99QT prolongation is a class effect of HDAC inhibitors, although the incidence may be lower than initially reported. Optimize serum potassium and magnesium levels prior to and during therapy [173, 205]

100RPLS is rare but serious. Monitor for headache, seizure, lethargy, and hypertension. Some fatal cases of hepatotoxicity have been reported. Serum hepatic enzyme elevations generally occur within 4–12 weeks. The most common hemorrhagic events were hematuria (4%), epistaxis (2%), hemoptysis (2%), and rectal hemorrhage. Rare cases of hypertensive crisis have been reported, most cases of hypertension within first 18 weeks of therapy. TMA including TTP and HUS can occur, generally within 3 months of treatment initiation [136, 158, 166, 209]

101Complications typically occur after several weeks of treatment during the induction phase. Clinical symptoms suggestive of pancreatitis have been reported to occur within 15 days of treatment [65]

102May cause severe immune-mediated adverse events including pneumonitis median onset 3.3 months (2 days to ~19 months) and is more common with prior thoracic radiation, hepatitis 1.3 months (8 days to 21.4 months), colitis 3.5 months (10 days to 16.2 months), autoimmune nephritis 5.1 months (12 days to 12.8 months), hyperthyroidism 1.4 months (1 day to ~22 months), and hypothyroidism 3.5 months (1 day to 19 months). May aggravate underlying autoimmune disorders. Management includes holding therapy, systemic corticosteroids, and +/− additional immunosuppressants (e.g., infliximab, mycophenolate, and vedolizumab). Consider PJP prophylaxis in patients with prolonged corticosteroid exposure [33, 148, 159, 160]

103Prophylactic folic acid and vitamin B12 supplementation should be provided while receiving pemetrexed to reduce the risk of hematologic toxicity. Renal damage ranges from acute to chronic kidney injury due to tubular and interstitial damage [70, 252]

104Consider HSV/VZV prophylaxis [105, 142]

105Prior anthracycline therapy or chest irradiation may increase the risk for cardiotoxicity (risk is lower than that seen with trastuzumab) [83, 235]

106Thromboprophylaxis with either aspirin or a LMWH should be considered for patients receiving pomalidomide in combination with chemotherapy and/or dexamethasone [49, 92].

107Vigilant monitoring for vascular events is recommended (i.e., MI, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease). Vascular occlusion/events can occur within weeks of starting therapy and is not dose dependent and requires interruption or permanent discontinuation of therapy. Arrhythmias, such as atrial fibrillation and symptomatic bradycardia, have been reported. Hypertension can be severe and should be managed as clinically indicated. Hepatotoxicity: median onset 3 months (range, less than 1 month to 47 months); may require treatment interruption or discontinuation. Bleeding can occur during therapy, particularly in patients with accelerated or blast phase disease and thrombocytopenia. RPLS has been reported. Monitor for headache, seizure, lethargy, and hypertension [53, 54, 139, 155, 247]

108Prophylactic folic acid and vitamin B12 supplementation are necessary to reduce hematologic toxicity [6]

Table 1G

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Ramucirumab

X

  

X

   

X

         

X

      

X

   

X

  

See Note 109

Regorafenib

X

      

X

         

X

 

X

X

       

X

 

X

See Note 110

Ribociclib

   

X

 

X

              

X

          

See Note 111

Rituximab

                 

X

         

X

  

X

See Note 112

Romidepsin

    

X

X

                     

X

   

See Note 113

Ruxolitinib

                            

X

  

See Note 114

Sipuleucel-T

   

X

                         

X

 

See Note 115

Sonidegib

               

X

       

X

     

X

 

See Note 116

Sorafenib

X

 

X

X

 

X

 

X

X

        

X

 

X

X

   

X

   

X

 

X

See Note 117

Sunitinib

X

 

X

X

 

X

 

X

X

          

X

X

   

X

   

X

  

See Note 118

Temozolomide

                    

X

      

X

   

See Note 119

Thalidomide

 

X

 

X

X

   

X

               

X

     

X

See Note 120

Thiotepa

X

                   

X

         

X

See Note 121

Tisagenlecleucel

X

X

X

 

X

   

X

      

X

    

X

    

X

 

X

   

See Note 122

Topotecan

        

X

         

X

            

See Note 123

Trabectiden

  

X

X

             

X

  

X

        

X

 

See Note 124

Trametinib

  

X

X

 

X

 

X

X

        

X

     

X

    

X

X

 

See Note 125

Trastuzumab

  

X

     

X

X

 

X

X

                  

See Note 126

Tretinoin (all-trans retinoic acid)

    

X

    

X

     

X

    

X

     

X

 

X

  

See Note 127

109Serious, sometimes fatal, MI, cardiac arrest, and CVA events have occurred in clinical trials. Can impair wound healing; therapy should be held prior to surgical procedures. Rates of hemorrhage or GI perforation unknown in patients on chronic NSAIDs or anticoagulation as many studies excluded these patients; therefore, use cautiously in combination with these agents [10, 71]

110Can impair wound healing. Discontinue 2 weeks prior to surgical procedures and resume once wound has healed. RPLS has been reported. Monitor for headache, seizure, lethargy, and hypertension [25, 158]

111Monitor and optimize serum potassium, calcium, phosphorus, and magnesium before and during therapy as electrolyte imbalances may occur to reduce risk of cardiotoxicity. Median onset of grade 3 or higher transaminase elevations ~2 months, with median time to resolution to grade 2 or lower of 24 days [104, 169]

112Abdominal pain, bowel obstruction, and perforation have been reported, with an average onset of symptoms ~6 days (1–77 days). JC virus infection resulting in PML has been reported. Median time to PML diagnosis 16 months following rituximab initiation and median time from last rituximab dose 5.5 months. HBV reactivation may occur during and up to 24 months after discontinuation of anti-CD20 antibodies. Patients on antiviral prophylaxis should continue for 6–12 months after completing treatment [32, 47, 106]

113QT prolongation is a class effect of HDAC inhibitors, although the incidence may be lower than initially reported. Optimize serum potassium, magnesium, and calcium levels prior to and during therapy. Viral reactivation has occurred during and within 30 days of initiation. Consider antiviral prophylaxis for patients with history of EBV or HBV [50, 205]

114Bacterial, mycobacterial, fungal, and viral infections have occurred including TB, PML, HSV/VZV and increased HBV viral load. Withdrawal syndrome can occur with abrupt discontinuation of treatment and is characterized by acute relapse of disease symptoms such as accelerated splenomegaly, worsening cytopenias, and sepsis-like syndrome. It can be managed with corticosteroids with a slow taper off [108]

115Vascular disorders including MI and stroke have been reported. Acute infusion reactions within 1 day of infusion have been reported [61].

116CPK elevations > grade 2 occur at a median of 13 weeks. CPK levels should be monitored at baseline and periodically during therapy. Rare cases of rhabdomyolysis have been reported [110, 233]

117HF, myocardial ischemia, and/or MI have been reported. Acute liver injury generally occurs a few days to up to 8 weeks after treatment initiation. Possible impaired wound healing. RPLS can rarely occur. Monitor for headache, seizure, lethargy, and hypertension [24, 216]

118RPLS can rarely occur. Case reports have occurred 1–34 weeks following treatment initiation. Monitor for headache, seizure, lethargy, and hypertension. Cardiac events including myocardial ischemia, MI, reductions in LVEF, and cardiac failure including death have occurred [56, 156, 158, 189]

119PJP prophylaxis is recommended [147]

120VTE, including ischemic heart disease, MI, and CVA have occurred in patients receiving thalidomide and dexamethasone. Thromboprophylaxis with either aspirin or a LMWH should be considered for patients receiving thalidomide in combination with chemotherapy and/or dexamethasone. Seizures and bradycardia have been reported in postmarketing data [51]

121Parent drug and/or metabolites may be partially excreted through the skin; severe blistering and desquamation can occur. As a result, patients should shower/bathe at least twice daily while receiving treatment and during the 48 h following therapy. Hepatotoxicity refers to VOD, which has been reported when high doses are used in combination with other chemotherapy as part of a conditioning regimen for stem cell transplant [58, 257]

122CRS: Median onset 3 days (1–22 days); median duration 8 days (1–36 days). Monitor for signs or symptoms of CRS for at least 4 weeks after treatment. Key manifestations include high fever, hypotension, and shortness of breath and may be associated with hepatic, renal, and cardiac dysfunction and coagulopathy. Risk factors for severe CRS are high pre-infusion tumor burden (>50% blasts in bone marrow), uncontrolled or accelerating tumor burden following lymphodepleting chemotherapy (fludarabine and cyclophosphamide), active infections, and/or inflammatory processes

ICANS: Most neurological toxicities occurred within 8 weeks and generally resolved within 12 days. Most common neurological toxicities include headache, encephalopathy, delirium, anxiety, and tremor. Fatal and serious cases of cerebral edema have occurred; other serious events included leukoencephalopathy and seizures.

Management of CRS with or without ICANS depends on grading or severity but includes supportive care, tocilizumab, and/or systemic corticosteroids. Grade 2 or higher ICANS without CRS should be treated with corticosteroids alone as there is insufficient data with tocilizumab in this setting. Other interleukin antagonists (e.g., siltuximab) and anti-T cell therapies are currently being evaluated.

Hypogammaglobulinemia secondary to B-cell aplasia may persist for up to 13 months and increase the risk for infections. PJP and HSV prophylaxis are recommended for at least 1 year after CAR-T cell therapy [143, 174]

123Post-marketing cases of ILD have been reported. Higher risk in patients with baseline interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs, and/or colony-stimulating factors [168]

124Grade 3 or 4 CPK elevations have been reported with a median onset of 2 months and resolving in ~2 weeks with dose interruption, reduction, discontinuation, or delay. Capillary leak syndrome has been reported [112]

125Cardiomyopathy: median onset in melanoma patients for single-agent trametinib ~2 months (2–22 weeks) and ~8 months (~1–25 months) when used in combination with dabrafenib, in patients with NSCLC 6.7 months (1.4–14.1 months). Pneumonitis: median time to initial presentation in melanoma patients ~5 months (2 to ~6 months). Risk of GI perforation is 0.3% when administered with dabrafenib. Grade 3/4 hyperglycemia reported when used in combination with dabrafenib [170]

126Highest incidence of cardiomyopathy in patients receiving trastuzumab with an anthracycline. Reversible upon discontinuation of trastuzumab [81, 96]

127Differentiation syndrome is commonly associated with the development of hyperleukocytosis, pulmonary edema, generalized edema, headache, bone pain, and renal failure; bimodal with peaks occurring in the first and third weeks after the start of therapy. Management includes steroids, with or without diuretics, and possible discontinuation of tretinoin, depending on severity [59, 153]

Table 1H

 

Neuro

Cardiac

Pulmonary

Renal

GI

Endocrine

Miscellaneous

Notes

 

Encephalopathy

Seizures

Heart failure

Thromboembolism

Arrhythmias

QT prolongation

Pericardial effusions

Severe hypertension

Pneumonitis

Pulmonary edema

Pulmonary hypertension

Pleural effusions

Organizing pneumonia

Diffuse alveolar hemorrhage

SIADH – hyponatremia

Renal failure

Hemorrhagic cystitis

Bowel perforation

Neutropenic colitis

Pancreatitis

Hepatotoxicity

Adrenal insufficiency

Hypophysitis

Hyperglycemia

Thyroid disorders

Cytokine release syndrome

Differentiation syndrome

Opportunistic infections

Bleeding (severe)

Rhabdomyolysis

Stevens-Johnson syndrome or Toxic epidermal necrolysis

 

Vandetanib

X

 

X

  

X

 

X

X

        

X

 

X

    

X

   

X

X

X

See Note 128

Vemurafenib

     

X

 

X

       

X

   

X

   

X

     

X

X

See Note 129

Vinblastine

              

X

                

See Note 130

Vincristine

X

X

            

X

  

X

             

See Note 131

Vinorelbine

X

    

X

  

X

     

X

    

X

X

          

See Note 132

Vismodegib

              

X

              

X

 

See Note 133

Vorinostat

   

X

 

X

                 

X

       

See Note 134

128Ischemic cerebrovascular events have been reported. RPLS has been reported – monitor for headache, seizure, lethargy, and hypertension. Optimize serum potassium, magnesium, and calcium levels prior to and during therapy. Rare cases of GI perforation. Due to long half-life (19 days), adverse reactions, including QT prolongation, may resolve slowly [214, 254]

129Optimize serum potassium, magnesium, and calcium levels prior to and during therapy to reduce risk of cardiotoxicity. AIN and ATN have been reported. Hypersensitivity: anaphylaxis and DRESS syndrome have been reported. Pancreatitis generally occurs within 2 weeks of treatment initiation [90, 157, 251, 255, 256]

130Paralytic ileus and obstruction may occur, although to a lesser extent than that observed with other vinca alkaloids

131Known to affect the cranial nerves resulting in ptosis, diplopia, and facial palsies. Paresthesias involving the hands and feet often occur within weeks of therapy and depending on severity and may require several months to resolve following drug discontinuation. Loss of motor involvement is possible as well (i.e., foot and hand drop, loss of deep tendon reflexes, weakness in the lower and upper extremities). Acute GI symptoms such as constipation and abdominal pain commonly occur within a few days of therapy, with more serious GI toxicities including adynamic ileus and bowel obstruction. SIADH-induced hyponatremia has led to seizures [200]

132May cause severe paralytic ileus [44, 188]

133May cause CPK elevations; rare occurrence of rhabdomyolysis [88]

134QT prolongation is a class effect of HDAC inhibitors, although the incidence may be lower than initially reported. Optimize serum potassium and magnesium levels prior to and during therapy [205]

5-FU, 5-fluorouracil; AIN, acute interstitial nephritis; ALK, anaplastic lymphoma kinase; ALT, alanine transaminase; AST, aspartate aminotransferase; ATN, acute tubular necrosis; BTK, Bruton’s tyrosine kinase; CD4, cluster of differentiation 4; CLL, chronic lymphocytic leukemia; CMV, cytomegalovirus; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CPK, creatine phosphokinase; CRS, cytokine release syndrome; CVA, cerebrovascular accident; DLCO, diffusing capacity of carbon monoxide; DRESS, drug reaction with eosinophilia and systemic symptoms; EBV, Epstein-Barr virus; EKG, electrocardiogram; FVC, forced vital capacity; GI, gastrointestinal; HBV, hepatitis B virus; HDAC, histone deacetylase; HF, heart failure; HLH, hemophagocytic lymphohistiocytosis; HMG-CoA, hydroxymethylglutaryl coenzyme A; HUS, hemolytic uremic syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; ILD, interstitial lung disease; IV, intravenous; JC virus, John Cunningham virus; LMWH, low molecular weight heparin; LVEF, left ventricular ejection fraction; MAS, macrophage activation syndrome; MI, myocardial infarction; NSCLC, non-small cell lung cancer; PD-1, programmed cell death 1; PJP, Pneumocystis jiroveci pneumonia; PK, pharmacokinetics; PML, progressive multifocal leukoencephalopathy; REMS, risk evaluation and mitigation strategy; RPLS, reversible posterior leukoencephalopathy syndrome; SJS, Stevens-Johnson syndrome; TB, tuberculosis; TBI, total body irradiation; TEN, toxic epidermal necrolysis; TMA, thrombotic microangiopathy; TSH, thyroid-stimulating hormone; TTP, thrombotic thrombocytopenic purpura; ULN, upper limit of normal; VOD, veno-occlusive disease; VTE, venous thromboembolism; VZV, varicella zoster virus

References

  1. 1.
    Abraxis Bioscience LLC. Abraxane (paclitaxel protein-bound particles) [package insert]. Summit; 2017.Google Scholar
  2. 2.
    Accord Healthcare Inc. Toposar (etoposide) [package insert]. Durham; 2014.Google Scholar
  3. 3.
    Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016;128(15):1940–3.  https://doi.org/10.1182/blood-2016-06-722991.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Aichberger KJ, Herndlhofer S, Schernthaner GH, Schillinger M, Mitterbauer-Hohendanner G, Sillaber C, Valent P. Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol. 2011;86(7):533–9.  https://doi.org/10.1002/ajh.22037.CrossRefPubMedGoogle Scholar
  5. 5.
    Aldoss I, Douer D, Behrendt CE, Chaudhary P, Mohrbacher A, Vrona J, Pullarkat V. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia. Eur J Haematol. 2016;96(4):375–80.  https://doi.org/10.1111/ejh.12600.CrossRefPubMedGoogle Scholar
  6. 6.
    Allos Therapeutics. Folotyn (pralatrexate) [package insert]. Westminister; 2009.Google Scholar
  7. 7.
    Amgen. Blincyto® (Blinatumomab) [package insert]. Thousand Oaks; 2017a.Google Scholar
  8. 8.
    Amgen. Vectibix (panitumumab) [package insert]. Thousand Oaks; 2017b.Google Scholar
  9. 9.
    Ariad Pharmaceuticals Inc. Alunbrig (brigatinib) [package insert]. Cambridge, MA; 2017.Google Scholar
  10. 10.
    Arnold D, Fuchs CS, Tabernero J, Ohtsu A, Zhu AX, Garon EB, Mackey JR, Paz-Ares L, Baron AD, Okusaka T, Yoshino T, Yoon HH, Das M, Ferry D, Zhang Y, Lin Y, Binder P, Sashegyi A, Chau I. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Ann Oncol. 2017;28(12):2932–42.  https://doi.org/10.1093/annonc/mdx514.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Asbury RF, Rosenthal SN, Descalzi ME, Ratcliffe RL, Arseneau JC. Hepatic veno-occlusive disease due to DTIC. Cancer. 1980;45(10):2670–4.CrossRefGoogle Scholar
  12. 12.
    AstraZeneca. Imfinzi (durvalumab) [package insert]. Wilmington; 2016.Google Scholar
  13. 13.
    AstraZeneca Pharmaceuticals. Calquence (acalabrutinib) [package insert]. Wilmington; 2017a.Google Scholar
  14. 14.
    AstraZeneca Pharmaceuticals. Lynparza (olaparib) capsules [package insert]. Wilmington; 2017b.Google Scholar
  15. 15.
    Au TH, Cavalieri CC, Stenehjem DD. Ceritinib: a primer for pharmacists. J Oncol Pharm Pract. 2017;23(8):602–14.  https://doi.org/10.1177/1078155216672315.CrossRefPubMedGoogle Scholar
  16. 16.
    Azambuja E, Fleck JF, Batista RG, Menna Barreto SS. Bleomycin lung toxicity: who are the patients with increased risk? Pulm Pharmacol Ther. 2005;18(5):363–6.  https://doi.org/10.1016/j.pupt.2005.01.007.CrossRefPubMedGoogle Scholar
  17. 17.
    AztraZeneca Pharmaceuticals LP. Iressa (gefitinib) [package insert]. Wilmington; 2015.Google Scholar
  18. 18.
    AztraZeneca Pharmaceuticals LP. Tagrisso (osimertinib) [package insert]. Wilmington; 2017.Google Scholar
  19. 19.
    Baker WJ, Royer GL Jr, Weiss RB. Cytarabine and neurologic toxicity. J Clin Oncol. 1991;9(4):679–93.  https://doi.org/10.1200/jco.1991.9.4.679.CrossRefPubMedGoogle Scholar
  20. 20.
    Baron M, Zini JM, Challan Belval T, Vignon M, Denis B, Alanio A, Malphettes M. Fungal infections in patients treated with ibrutinib: two unusual cases of invasive aspergillosis and cryptococcal meningoencephalitis. Leuk Lymphoma. 2017;58(12):2981–2.  https://doi.org/10.1080/10428194.2017.1320710.CrossRefPubMedGoogle Scholar
  21. 21.
    Baxter. Cyclophosphamide Injection [package insert]. Deerfield; 2015.Google Scholar
  22. 22.
    Baxter Healthcare Corp. Ifex (ifosfamide) [prescribing information]. Deerfield; 2014.Google Scholar
  23. 23.
    Bayer Healthcare Pharmaceuticals Inc. Aliqopa (copanlisib) [package insert]. Whippany; 2017a.Google Scholar
  24. 24.
    Bayer Healthcare Pharmaceuticals Inc. Nexevar (sorafenib) [package insert]. Whippany; 2017b.Google Scholar
  25. 25.
    Bayer HealthCare Pharmaceuticals Inc. Stivarga (regorafenib) [package insert]. Whippany; 2017c.Google Scholar
  26. 26.
    Bedford Laboratories. Adriamycin (doxorubicin HCL) [package insert]. Bedford; 2012.Google Scholar
  27. 27.
    Bedford Laboratories. Daunorubicin hydrochloride injection [package insert]. Bedford; 2013.Google Scholar
  28. 28.
    Bergeron A, Rea D, Levy V, Picard C, Meignin V, Tamburini J, Bruzzoni-Giovanelli H, Calvo F, Tazi A, Rousselot P. Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series. Am J Respir Crit Care Med. 2007;176(8):814–8.  https://doi.org/10.1164/rccm.200705-715CR.CrossRefPubMedGoogle Scholar
  29. 29.
    Bielopolski D, Evron E, Moreh-Rahav O, Landes M, Stemmer SM, Salamon F. Paclitaxel-induced pneumonitis in patients with breast cancer: case series and review of the literature. J chemother (Florence, Italy). 2017;29(2):113–7.  https://doi.org/10.1179/1973947815y.0000000029.CrossRefGoogle Scholar
  30. 30.
    Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thrombotic microangiopathy with targeted cancer agents. Clin Cancer Res. 2011;17(18):5858–66.  https://doi.org/10.1158/1078-0432.Ccr-11-0804.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Boehringer-ingelheim. Gilotrif (afatinib) [package insert]. Ridgfield; 2018.Google Scholar
  32. 32.
    Bohra C, Sokol L, Dalia S. Progressive multifocal leukoencephalopathy and monoclonal antibodies: a review. Cancer Control. 2017;24(4):1073274817729901.  https://doi.org/10.1177/1073274817729901.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018a;36:1714–68.  https://doi.org/10.1200/jco.2017.77.6385.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018b;36:1714–68. (Published online: February 14, 2018).CrossRefGoogle Scholar
  35. 35.
    Bristol-Myers Squibb. Ixempra (ixabepilone) [package insert]. Princeton; 2007.Google Scholar
  36. 36.
    Bristol-Myers Squibb. Opdivo (nivolumab) [package insert]. Princeton; 2018.Google Scholar
  37. 37.
    Bristol-Myers Squibb Company. Blenoxane (bleomycin) [package insert]. Princeton; 2010a.Google Scholar
  38. 38.
    Bristol-Myers Squibb Company. Platinol (cisplatin) [package insert]. Princeton; 2010b.Google Scholar
  39. 39.
    Bristol-Myers Squibb Company. Sprycel (dasatinib) [package insert]. Princeton; 2017a.Google Scholar
  40. 40.
    Bristol-Myers Squibb Company. Yervoy (ipilimumab) [package insert]. Princeton; 2017b.Google Scholar
  41. 41.
    Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374(4):323–32.  https://doi.org/10.1056/NEJMoa1509981.CrossRefPubMedGoogle Scholar
  42. 42.
    Camacho LH. CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Cancer Med. 2015;4(5):661–72.  https://doi.org/10.1002/cam4.371.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992;327(21):1478–84.  https://doi.org/10.1056/nejm199211193272102.CrossRefPubMedGoogle Scholar
  44. 44.
    Canzler U, Schmidt-Gohrich UK, Bergmann S, Hanseroth K, Gatzweiler A, Distler W. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by vinorelbine treatment of metastatic breast cancer. Onkologie. 2007;30(8–9):455–6.  https://doi.org/10.1159/000105143.CrossRefPubMedGoogle Scholar
  45. 45.
    Carilli A, Favis G, Sundharkrishnan L, Hajdenberg J. Severe dermatologic reactions with bendamustine: a case series. Case Rep Oncol. 2014;7(2):465–70.  https://doi.org/10.1159/000365324.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Carron PL, Cousin L, Caps T, Belle E, Pernet D, Neidhardt A, Capellier G. Gemcitabine-associated diffuse alveolar hemorrhage. Intensive Care Med. 2001;27(9):1554.  https://doi.org/10.1007/s001340101037.CrossRefPubMedGoogle Scholar
  47. 47.
    Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, Laubach J, Bawn SD, Gordon LI, Winter JN, Furman RR, Vose JM, Zelenetz AD, Mamtani R, Raisch DW, Dorshimer GW, Rosen ST, Muro K, Gottardi-Littell NR, Talley RL, Sartor O, Green D, Major EO, Bennett CL. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood. 2009;113(20):4834–40.  https://doi.org/10.1182/blood-2008-10-186999.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Carson KR, Newsome SD, Kim EJ, Wagner-Johnston ND, von Geldern G, Moskowitz CH, Moskowitz AJ, Rook AH, Jalan P, Loren AW, Landsburg D, Coyne T, Tsai D, Raisch DW, Norris LB, Bookstaver PB, Sartor O, Bennett CL. Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. Cancer. 2014;120(16):2464–71.  https://doi.org/10.1002/cncr.28712.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Celegene Corporation. Pomalyst (pomalidomide) [package insert]. Summit; 2018.Google Scholar
  50. 50.
    Celgene Corporation. 2016 Istodax (romidepsin) [package insert]. Summit; 2018.Google Scholar
  51. 51.
    Celgene Corporation. Thalomid (thalidomide) [package insert]. Summit; 2017.Google Scholar
  52. 52.
    Ciurea SO, Andersson BS. Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15(5):523–36.  https://doi.org/10.1016/j.bbmt.2008.12.489.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MW, Talpaz M. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075–88.  https://doi.org/10.1056/NEJMoa1205127.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Muller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783–96.  https://doi.org/10.1056/NEJMoa1306494.CrossRefPubMedGoogle Scholar
  55. 55.
    Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boque C, Shah NP, Chuah C, Casanova L, Bradley-Garelik B, Manos G, Hochhaus A. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naive chronic myeloid leukemia patients trial. J Clin Oncol. 2016;34(20):2333–40.  https://doi.org/10.1200/jco.2015.64.8899.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Costa R, Costa R, Costa R, Junior GM, Cartaxo HQ, de Barros AC. Reversible posterior encephalopathy syndrome secondary to sunitinib. Case Rep Oncol Med. 2014;2014:952624.  https://doi.org/10.1155/2014/952624.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Cowman S, Stebbing J, Tuthill M. Large bowel perforation associated with capecitabine treatment for breast cancer. Ann Oncol. 2008;19(8):1510–1.  https://doi.org/10.1093/annonc/mdn397.CrossRefPubMedGoogle Scholar
  58. 58.
    Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22(3):400–9.  https://doi.org/10.1016/j.bbmt.2015.09.024.CrossRefPubMedGoogle Scholar
  59. 59.
    De Botton S, Dombret H, Sanz M, Miguel JS, Caillot D, Zittoun R, Gardembas M, Stamatoulas A, Conde E, Guerci A, Gardin C, Geiser K, Makhoul DC, Reman O, de la Serna J, Lefrere F, Chomienne C, Chastang C, Degos L, Fenaux P. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1998;92(8):2712–8.PubMedGoogle Scholar
  60. 60.
    de Forni M, Malet-Martino MC, Jaillais P, Shubinski RE, Bachaud JM, Lemaire L, Canal P, Chevreau C, Carrie D, Soulie P, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol. 1992;10(11):1795–801.  https://doi.org/10.1200/jco.1992.10.11.1795.CrossRefPubMedGoogle Scholar
  61. 61.
    Dendreon Corporation. Provenge (sipuleucel-T) [package insert]. Seattle; 2014.Google Scholar
  62. 62.
    Dhesi S, Chu MP, Blevins G, Paterson I, Larratt L, Oudit GY, Kim DH. Cyclophosphamide-induced cardiomyopathy: a case report, review, and recommendations for management. J Invest Med High Impact Case Rep. 2013;1(1):2324709613480346.  https://doi.org/10.1177/2324709613480346.CrossRefGoogle Scholar
  63. 63.
    Dimopoulos MA, Roussou M, Gavriatopoulou M, Psimenou E, Ziogas D, Eleutherakis-Papaiakovou E, Fotiou D, Migkou M, Kanellias N, Panagiotidis I, Ntalianis A, Papadopoulou E, Stamatelopoulos K, Manios E, Pamboukas C, Kontogiannis S, Terpos E, Kastritis E. Cardiac and renal complications of carfilzomib in patients with multiple myeloma. Blood Adv. 2017;1(7):449–54.  https://doi.org/10.1182/bloodadvances.2016003269.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Domchek SM, Aghajanian C, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Loman N, Robertson JD, Mann H, Kaufman B. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol. 2016;140(2):199–203.  https://doi.org/10.1016/j.ygyno.2015.12.020.CrossRefPubMedGoogle Scholar
  65. 65.
    Douer D, Aldoss I, Lunning MA, Burke PW, Ramezani L, Mark L, Vrona J, Park JH, Tallman MS, Avramis VI, Pullarkat V, Mohrbacher AM. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–11.  https://doi.org/10.1200/jco.2013.50.2708.CrossRefPubMedGoogle Scholar
  66. 66.
    Dutcher JP, Schwartzentruber DJ, Kaufman HL, Agarwala SS, Tarhini AA, Lowder JN, Atkins MB. High dose interleukin-2 (Aldesleukin) – expert consensus on best management practices-2014. J Immuno Ther Cancer. 2014;2(1):26.  https://doi.org/10.1186/s40425-014-0026-0.CrossRefGoogle Scholar
  67. 67.
    Eisai Inc. Lenvima (lenvatinib) capsules [package insert]. Woodcliff Lake; 2017.Google Scholar
  68. 68.
    Eli Lilly and Company. Portrazza (necitumumab) [package insert]. Indianapolis; 2015.Google Scholar
  69. 69.
    Eli Lilly and Company. Erbitux (cetuximab) [package insert]. Indianapolis; 2016Google Scholar
  70. 70.
    Eli Lilly and Company. Alimta (pemetrexed) [package insert]. Indianapolis; 2017a.Google Scholar
  71. 71.
    Eli Lilly and Company. Cyramza (ramucirumab) [package insert]. Indianapolis; 2017bGoogle Scholar
  72. 72.
    Eli Lilly and Company. Gemzar (gemcitabine) [package insert]. Indianapolis; 2017c.Google Scholar
  73. 73.
    EMD Serono. Bavencio (avelumab) [package insert]. Rockland; 2017.Google Scholar
  74. 74.
    EMD Serono. Novantrone (Mitoxantrone) [package insert]. Rockland; 2008.Google Scholar
  75. 75.
    Eremina V, Jefferson JA, Kowalewska J, Hochster H, Haas M, Weisstuch J, Richardson C, Kopp JB, Kabir MG, Backx PH, Gerber HP, Ferrara N, Barisoni L, Alpers CE, Quaggin SE. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358(11):1129–36.  https://doi.org/10.1056/NEJMoa0707330.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Exelixis Inc. Cometriq (cabozantinib) [package insert]. South San Francisco; 2017.Google Scholar
  77. 77.
    Faderl S, Ravandi F, Huang X, Garcia-Manero G, Ferrajoli A, Estrov Z, Borthakur G, Verstovsek S, Thomas DA, Kwari M, Kantarjian HM. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008;112(5):1638–45.  https://doi.org/10.1182/blood-2007-11-124602.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Feinberg WM, Swenson MR. Cerebrovascular complications of L-asparaginase therapy. Neurology. 1988;38(1):127–33.CrossRefGoogle Scholar
  79. 79.
    Gass-Jegu F, Gschwend A, Gairard-Dory AC, Mennecier B, Tebacher-Alt M, Gourieux B, Quoix E. Gastrointestinal perforations in patients treated with erlotinib: a report of two cases with fatal outcome and literature review. Lung Cancer (Amsterdam, Netherlands). 2016;99:76–8.  https://doi.org/10.1016/j.lungcan.2016.06.012.CrossRefGoogle Scholar
  80. 80.
    Geiser CF, Bishop Y, Jaffe N, Furman L, Traggis D, Frei E 3rd. Adverse effects of intrathecal methotrexate in children with acute leukemia in remission. Blood. 1975;45(2):189–95.PubMedGoogle Scholar
  81. 81.
    Genentech Inc. Herceptin (trastuzumab) [package insert]. South San Francisco; 2017a.Google Scholar
  82. 82.
    Genentech Inc. Kadcyla (ado-traztuzumab emtansine) [package insert]. South San Francisco; 2017b.Google Scholar
  83. 83.
    Genentech Inc. Perjeta (pertuzumab) [package insert]. South San Francisco; 2017c.Google Scholar
  84. 84.
    Genentech Inc. Cotellic (cobimetinib) [package insert]. South San Francisco; 2018.Google Scholar
  85. 85.
    Genentech USA Inc. Xeloda (capecitabine) [package insert]. South San Francisco; 2016Google Scholar
  86. 86.
    Genentech USA Inc. Alecensa (alectinib) [package insert] South San Francisco; 2017a.Google Scholar
  87. 87.
    Genentech USA Inc. Avastin (bevacizumab) [package insert]. South San Francisco; 2017b.Google Scholar
  88. 88.
    Genentech USA Inc. Erivedge (vismodegib) [package insert]. South San Francisco; 2017c.Google Scholar
  89. 89.
    Genentech USA Inc. Tecentriq (atezolizumab) [package insert]. South San Francisco; 2017d.Google Scholar
  90. 90.
    Genentech USA Inc. Zelboraf (vemurafenib) [package insert]. South San Francisco; 2017e.Google Scholar
  91. 91.
    Genzyme Corporation. Lemtrada (alemtuzumab) [package insert]. Cambridge, MA; 2017.Google Scholar
  92. 92.
    Geyer HL, Viggiano RW, Lacy MQ, Witzig TE, Leslie KO, Mikhael JR, Stewart K. Acute lung toxicity related to pomalidomide. Chest. 2011;140(2):529–33.  https://doi.org/10.1378/chest.10-2082.CrossRefPubMedGoogle Scholar
  93. 93.
    Gilead Sciences. Zydelig (idelalisib) [package insert]. Foster City; 2016.Google Scholar
  94. 94.
    Giles FJ, Mauro MJ, Hong F, Ortmann CE, McNeill C, Woodman RC, Hochhaus A, le Coutre PD, Saglio G. Rates of peripheral arterial occlusive disease in patients with chronic myeloid leukemia in the chronic phase treated with imatinib, nilotinib, or non-tyrosine kinase therapy: a retrospective cohort analysis. Leukemia. 2013;27(6):1310–5.  https://doi.org/10.1038/leu.2013.69.CrossRefPubMedGoogle Scholar
  95. 95.
    GlaxoSmithKline. Alkeran®(melphalan) [package insert]. Research Triangle Park; 2012.Google Scholar
  96. 96.
    Goldhar HA, Yan AT, Ko DT, Earle CC, Tomlinson GA, Trudeau ME, Krahn MD, Krzyzanowska MK, Pal RS, Brezden-Masley C, Gavura S, Lien K, Chan KK. The temporal risk of heart failure associated with adjuvant trastuzumab in breast cancer patients: a population study. J Natl Cancer Inst. 2016;108(1).  https://doi.org/10.1093/jnci/djv301.CrossRefGoogle Scholar
  97. 97.
    Grellety T, Houede N, Hoepffner JL, Riviere J, Merino C, Lieutenant V, Gross-Goupil M, Richaud P, Dupin C, Sargos P, Roubaud G. Hemorrhagic cystitis in patients treated with cabazitaxel: a radiation recall syndrome? Ann Oncol. 2014;25(6):1248–9.  https://doi.org/10.1093/annonc/mdu132.CrossRefPubMedGoogle Scholar
  98. 98.
    Hamnvik OP, Larsen PR, Marqusee E. Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst. 2011;103(21):1572–87.  https://doi.org/10.1093/jnci/djr373.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Haskell CM, Canellos GP, Leventhal BG, Carbone PP, Block JB, Serpick AA, Selawry OS. l-asparaginase: therapeutic and toxic effects in patients with neoplastic disease. N Engl J Med. 1969;281(19):1028–34.  https://doi.org/10.1056/nejm196911062811902.CrossRefPubMedGoogle Scholar
  100. 100.
    Helman DL Jr, Byrd JC, Ales NC, Shorr AF. Fludarabine-related pulmonary toxicity: a distinct clinical entity in chronic lymphoproliferative syndromes. Chest. 2002;122(3):785–90.CrossRefGoogle Scholar
  101. 101.
    Heritage Pharmaceuticals. BiCNU (carmustine) [package insert]. Eatontown; 2017.Google Scholar
  102. 102.
    Herzig RH, Hines JD, Herzig GP, Wolff SN, Cassileth PA, Lazarus HM, Adelstein DJ, Brown RA, Coccia PF, Strandjord S, et al. Cerebellar toxicity with high-dose cytosine arabinoside. J Clin Oncol. 1987;5(6):927–32.  https://doi.org/10.1200/jco.1987.5.6.927.CrossRefPubMedGoogle Scholar
  103. 103.
    Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre PD, Etienne G, Dorlhiac-Llacer PE, Clark RE, Flinn IW, Nakamae H, Donohue B, Deng W, Dalal D, Menssen HD, Kantarjian HM. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044–54.  https://doi.org/10.1038/leu.2016.5.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, Andre F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O’Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48.  https://doi.org/10.1056/NEJMoa1609709.CrossRefPubMedGoogle Scholar
  105. 105.
    Hospira. Nipent (pentostatin for injection) [package insert]. Lake Forest; 2018.Google Scholar
  106. 106.
    Hwang JP, Somerfield MR, Alston-Johnson DE, Cryer DR, Feld JJ, Kramer BS, Sabichi AL, Wong SL, Artz AS. Hepatitis B virus screening for patients with cancer before therapy: American society of clinical oncology provisional clinical opinion update. J Clin Oncol. 2015;33(19):2212–20.  https://doi.org/10.1200/jco.2015.61.3745.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Ikeda S, Sekine A, Kato T, Yoshida M, Ogata R, Baba T, Nagahama K, Okudela K, Ogura T. Diffuse alveolar hemorrhage as a fatal adverse effect of bevacizumab: an autopsy case. Jpn J Clin Oncol. 2014;44(5):497–500.  https://doi.org/10.1093/jjco/hyu023.CrossRefPubMedGoogle Scholar
  108. 108.
    Incyte Corp. Jakafi (ruxolitinib) [package insert]. Wilmington; 2011.Google Scholar
  109. 109.
    Ingenus Pharmaceuticals. Carboplatin [package insert]. Orlando; 2017.Google Scholar
  110. 110.
    Jain S, Song R, Xie J. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. Onco Targets Ther. 2017;10:1645–53.  https://doi.org/10.2147/ott.S130910.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Janssen Biotech. Darzalex (daratumumab) [package insert]. Horsham; 2017.Google Scholar
  112. 112.
    Janssen Products. Yondelis (trabectedin) [package insert]. Horsham; 2015.Google Scholar
  113. 113.
    Janssen Products. Doxil (doxorubicin HCl liposome injection) [package insert]. Horsahm; 2016.Google Scholar
  114. 114.
    Jazz Pharmaceuticals. VYXEOS (daunorubicin and cytarabine) liposome [package insert]. Palo Alto; 2018.Google Scholar
  115. 115.
    Jazz Pharmaceuticals. Erwinaze intramuscular injection, intravenous injection (asparaginase Erwinia chrysanthemi intramuscular injection, intravenous injection) [package insert]. Palo Alto; 2016.Google Scholar
  116. 116.
    Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55.  https://doi.org/10.1056/NEJMoa1609214.CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Johnston PB, Bondly C, Micallef IN. Ibritumomab tiuxetan for non-Hodgkin’s lymphoma. Expert Rev Anticancer Ther. 2006;6(6):861–9.  https://doi.org/10.1586/14737140.6.6.861.CrossRefPubMedGoogle Scholar
  118. 118.
    Jolson HM, Bosco L, Bufton MG, Gerstman BB, Rinsler SS, Williams E, Flynn B, Simmons WD, Stadel BV, Faich GA, et al. Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine. J Natl Cancer Inst. 1992;84(7):500–5.CrossRefGoogle Scholar
  119. 119.
    June Therapeutics. Juno Therapeutics and Celgene corporation release additional data from TRANSCEND trial of JCAR017 in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. 2017, viewed 11 March 2018. http://ir.celgene.com/releasedetail.cfm?releaseid=1051336
  120. 120.
    Junpaparp P, Sharma B, Samiappan A, Rhee JH, Young KR. Everolimus-induced severe pulmonary toxicity with diffuse alveolar hemorrhage. Ann Am Thorac Soc. 2013;10(6):727–9.  https://doi.org/10.1513/AnnalsATS.201309-332LE.CrossRefPubMedGoogle Scholar
  121. 121.
    Kadia TM, Gandhi V. Nelarabine in the treatment of pediatric and adult patients with T-cell acute lymphoblastic leukemia and lymphoma. Expert Rev Hematol. 2017;10(1):1–8.  https://doi.org/10.1080/17474086.2017.1262757.CrossRefPubMedGoogle Scholar
  122. 122.
    Kanie K, Iguchi G, Bando H, Fujita Y, Odake Y, Yoshida K, Matsumoto R, Fukuoka H, Ogawa W, Takahashi Y. Two cases of atezolizumab-induced hypophysitis. J Endocr Soc. 2018;2(1):91–5.  https://doi.org/10.1210/js.2017-00414.CrossRefPubMedGoogle Scholar
  123. 123.
    Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, Merchant AA, Fujishima N, Uchida T, Calbacho M, Ejduk AA, O’Brien SM, Jabbour EJ, Zhang H, Sleight BJ, Vandendries ER, Marks DI. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4(8):e387–98.  https://doi.org/10.1016/s2352-3026(17)30103-5.CrossRefPubMedGoogle Scholar
  124. 124.
    Kebriaei P, Wilhelm K, Ravandi F, Brandt M, de Lima M, Ciurea S, Worth L, O'Brien S, Thomas D, Champlin RE, Kantarjian H. Feasibility of allografting in patients with advanced acute lymphoblastic leukemia after salvage therapy with inotuzumab ozogamicin. Clin Lymphoma Myeloma Leuk. 2013;13(3):296–301.  https://doi.org/10.1016/j.clml.2012.12.003.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, Kelly V, Brummendorf TH. Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 2012;119(15):3403–12.  https://doi.org/10.1182/blood-2011-11-390120.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Kieslich M, Porto L, Lanfermann H, Jacobi G, Schwabe D, Bohles H. Cerebrovascular complications of l-asparaginase in the therapy of acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2003;25(6):484–7.CrossRefGoogle Scholar
  127. 127.
    Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodriguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017;35(22):2490–8.  https://doi.org/10.1200/jco.2016.71.5904.CrossRefPubMedGoogle Scholar
  128. 128.
    Kite Pharma Inc. Yescarta (axicabtagene ciloleucel) [package insert]. Santa Monica; 2017.Google Scholar
  129. 129.
    Krause AS, Weihrauch MR, Bode U, Fleischhack G, Elter T, Heuer T, Engert A, Diehl V, Josting A. Carboxypeptidase-G2 rescue in cancer patients with delayed methotrexate elimination after high-dose methotrexate therapy. Leuk Lymphoma. 2002;43(11):2139–43.  https://doi.org/10.1080/1042819021000032953.CrossRefPubMedGoogle Scholar
  130. 130.
    Kuhlen M, Bleckmann K, Moricke A, Schrappe M, Vieth S, Escherich G, Bronsema A, Vonalt A, Queudeville M, Zwaan CM, Ebinger M, Debatin KM, Klingebiel T, Koscielniak E, Rossig C, Burkhardt B, Kolb R, Eckert C, Borkhardt A, von Stackelberg A, Chen-Santel C. Neurotoxic side effects in children with refractory or relapsed T-cell malignancies treated with nelarabine based therapy. Br J Haematol. 2017;179(2):272–83.  https://doi.org/10.1111/bjh.14877.CrossRefPubMedGoogle Scholar
  131. 131.
    Lambertini M, Del Mastro L, Gardin G, Levaggi A, Bighin C, Giraudi S, Pronzato P. Stevens-Johnson syndrome after treatment with bendamustine. Leuk Res. 2012;36(7):e153–4.  https://doi.org/10.1016/j.leukres.2012.03.006.CrossRefPubMedGoogle Scholar
  132. 132.
    Lancet JE, Uy G, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Chiarella M, Louie AC, Medeiros BC (Abstract 7000) Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol. 2016; 34(15 Suppl): p. 7000.CrossRefGoogle Scholar
  133. 133.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34.  https://doi.org/10.1056/NEJMoa1504030.CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Latagliata R, Breccia M, Fava C, Stagno F, Tiribelli M, Luciano L, Gozzini A, Gugliotta G, Annunziata M, Cavazzini F, Ferrero D, Musto P, Capodanno I, Iurlo A, Visani G, Crugnola M, Calistri E, Castagnetti F, Vigneri P, Alimena G. Incidence, risk factors and management of pleural effusions during dasatinib treatment in unselected elderly patients with chronic myelogenous leukaemia. Hematol Oncol. 2013;31(2):103–9.  https://doi.org/10.1002/hon.2020.CrossRefPubMedGoogle Scholar
  135. 135.
    Le Coutre P, Rea D, Abruzzese E, Dombret H, Trawinska MM, Herndlhofer S, Dorken B, Valent P. Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst. 2011;103(17):1347–8.  https://doi.org/10.1093/jnci/djr292.CrossRefPubMedGoogle Scholar
  136. 136.
    Lenihan DJ, Kowey PR. Overview and management of cardiac adverse events associated with tyrosine kinase inhibitors. Oncologist. 2013;18(8):900–8.  https://doi.org/10.1634/theoncologist.2012-0466.CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Lilly USA LLC. Verzenio (abemaciclib) [package insert]. Indianapolis; 2017.Google Scholar
  138. 138.
    Linette DC, McGee KH, McFarland JA. Mitomycin-induced pulmonary toxicity: case report and review of the literature. Ann Pharmacother. 1992;26(4):481–4.  https://doi.org/10.1177/106002809202600404.CrossRefPubMedGoogle Scholar
  139. 139.
    Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, Etienne G, Nicolini FE, le Coutre P, Clark RE, Stenke L, Andorsky D, Oehler V, Lustgarten S, Rivera VM, Clackson T, Haluska FG, Baccarani M, Cortes JE, Guilhot F, Hochhaus A, Hughes T, Kantarjian HM, Shah NP, Talpaz M, Deininger MW. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(5):612–21.  https://doi.org/10.1016/s1470-2045(16)00080-2.CrossRefPubMedGoogle Scholar
  140. 140.
    Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Somerfield MR, Falanga A. Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33(6):654–6.  https://doi.org/10.1200/jco.2014.59.7351.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Malalagama GN, Chryssidis S, Parnis FX. CT findings in patients with Cabazitaxel induced pelvic pain and haematuria: a case series. Cancer Imaging. 2017;17(1):17.  https://doi.org/10.1186/s40644-017-0119-3.CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, Belinson J. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol. 1999;17(4):1141.  https://doi.org/10.1200/jco.1999.17.4.1141.CrossRefPubMedGoogle Scholar
  143. 143.
    Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):439–48.  https://doi.org/10.1056/NEJMoa1709866.CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Mayne Pharma Limited. Epirubicin hydrochloride [package insert]. Paramus; 2006.Google Scholar
  145. 145.
    McKoy JM, Angelotta C, Bennett CL, Tallman MS, Wadleigh M, Evens AM, Kuzel TM, Trifilio SM, Raisch DW, Kell J, DeAngelo DJ, Giles FJ. Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. Leuk Res. 2007;31(5):599–604.  https://doi.org/10.1016/j.leukres.2006.07.005.CrossRefPubMedGoogle Scholar
  146. 146.
    McMullen JR, Boey EJ, Ooi JY, Seymour JF, Keating MJ, Tam CS. Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood. 2014;124(25):3829–30.  https://doi.org/10.1182/blood-2014-10-604272.CrossRefPubMedGoogle Scholar
  147. 147.
    Merck & Co. Temodar (temozolomide) [package insert]. Whitehouse Station; 2017a.Google Scholar
  148. 148.
    Merck & Co. Keytruda (pembrolizumab) [package insert]. Whitehouse Station; 2017b.Google Scholar
  149. 149.
    Meyer CC, Calis KA, Burke LB, Walawander CA, Grasela TH. Symptomatic cardiotoxicity associated with 5-fluorouracil. Pharmacotherapy. 1997;17(4):729–36.PubMedGoogle Scholar
  150. 150.
    Millennium Pharmaceuticals Inc. Velcade (bortezomib) [package insert]. Cambridge, MA; 2017.Google Scholar
  151. 151.
    Mitani S, Kadowaki S, Komori A, Sugiyama K, Narita Y, Taniguchi H, Ura T, Ando M, Sato Y, Yamaura H, Inaba Y, Ishihara M, Tanaka T, Tajika M, Muro K. Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: a case series and review of the literature. Medicine. 2017;96(22):e6874.  https://doi.org/10.1097/md.0000000000006874.CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Montani D, Bergot E, Gunther S, Savale L, Bergeron A, Bourdin A, Bouvaist H, Canuet M, Pison C, Macro M, Poubeau P, Girerd B, Natali D, Guignabert C, Perros F, O’Callaghan DS, Jais X, Tubert-Bitter P, Zalcman G, Sitbon O, Simonneau G, Humbert M. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125(17):2128–37.  https://doi.org/10.1161/circulationaha.111.079921.CrossRefPubMedGoogle Scholar
  153. 153.
    Montesinos P, Bergua JM, Vellenga E, Rayon C, Parody R, de la Serna J, Leon A, Esteve J, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Diaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775–83.  https://doi.org/10.1182/blood-2008-07-168617.CrossRefPubMedGoogle Scholar
  154. 154.
    Moskovitz M, Wollner M, Haim N. Oxaliplatin-induced pulmonary toxicity in gastrointestinal malignancies: two case reports and review of the literature. Case Rep Oncol Med. 2015;2015:341064.  https://doi.org/10.1155/2015/341064.CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Moslehi JJ, Deininger M. Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia. J Clin Oncol. 2015;33(35):4210–8.  https://doi.org/10.1200/jco.2015.62.4718.CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Motzer RJ, Hutson TE, Olsen MR, Hudes GR, Burke JM, Edenfield WJ, Wilding G, Agarwal N, Thompson JA, Cella D, Bello A, Korytowsky B, Yuan J, Valota O, Martell B, Hariharan S, Figlin RA. Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma. J Clin Oncol. 2012;30(12):1371–7.  https://doi.org/10.1200/jco.2011.36.4133.CrossRefPubMedGoogle Scholar
  157. 157.
    Munch M, Peuvrel L, Brocard A, Saint Jean M, Khammari A, Dreno B, Quereux G. Early-onset vemurafenib-induced DRESS syndrome. Dermatology (Basel, Switzerland). 2016;232(1):126–8.  https://doi.org/10.1159/000439272.CrossRefGoogle Scholar
  158. 158.
    Myint ZW, Sen JM, Watts NL, Druzgal TJ, Nathan BR, Ward MD, Boyer JE, Fracasso PM. Reversible posterior leukoencephalopathy syndrome during regorafenib treatment: a case report and literature review of reversible posterior leukoencephalopathy syndrome associated with multikinase inhibitors. Clin Colorectal Cancer. 2014;13(2):127–30.  https://doi.org/10.1016/j.clcc.2013.12.003.CrossRefPubMedGoogle Scholar
  159. 159.
    Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375–91.  https://doi.org/10.1093/annonc/mdv383.CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J, Voss MH, Rudin CM, Rizvi H, Hou X, Rodriguez K, Albano M, Gordon RA, Leduc C, Rekhtman N, Harris B, Menzies AM, Guminski AD, Carlino MS, Kong BY, Wolchok JD, Postow MA, Long GV, Hellmann MD. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709–17.  https://doi.org/10.1200/jco.2016.68.2005.CrossRefPubMedGoogle Scholar
  161. 161.
    Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017;377(26):2531–44.  https://doi.org/10.1056/NEJMoa1707447.CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Nesher L, Rolston KV. Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy. Clin Infect Dis. 2013;56(5):711–7.  https://doi.org/10.1093/cid/cis998.CrossRefPubMedGoogle Scholar
  163. 163.
    NIH NCI. A to Z list of cancer drugs; 2018. Viewed 20 March 2018. https://www.cancer.gov/about-cancer/treatment/drugs
  164. 164.
    Novartis Pharmaceutical Co. Afinitor and Afinitor Disperz (everolimus) [package insert]. East Hanover; 2017a.Google Scholar
  165. 165.
    Novartis Pharmaceutical Co. Tykerb (Lapatinib) [package insert]. East Hanover; 2017b.Google Scholar
  166. 166.
    Novartis Pharmaceutical Co. Votrient (pazopanib) [package insert]. East Hanover; 2017c.Google Scholar
  167. 167.
    Novartis Pharmaceutical Co. Zykadia (ceritinib) [package insert] East Hanover; 2017d.Google Scholar
  168. 168.
    Novartis Pharmaceuticals. Hycamtin (topotecan oral capsules) [package insert]. East Hanover; 2016.Google Scholar
  169. 169.
    Novartis Pharmaceuticals. Kasqali (ribociclib) [package insert]. East Hanover; 2017a.Google Scholar
  170. 170.
    Novartis Pharmaceuticals. Mekinist (trametinib) [package insert]. East Hanover; 2017b.Google Scholar
  171. 171.
    Novartis Pharmaceuticals. Tafinlar (dabrafenib) [package insert]. East Hanover; 2017c.Google Scholar
  172. 172.
    Novartis Pharmaceuticals. Tasigna oral capsules, nilotinib oral capsules [package insert]. East Hanover; 2018.Google Scholar
  173. 173.
    Novartis Pharmaceuticals Corporation. Farydak (panobinostat) [package insert]. East Hanover; 2016.Google Scholar
  174. 174.
    Novartis Pharmaceuticals Corporation. Kymriah (tisagenlecleucel) [prescribing information]. East Hanover; 2017.Google Scholar
  175. 175.
    Ohnishi K, Sakai F, Kudoh S, Ohno R. Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate. Leukemia. 2006;20(6):1162–4.  https://doi.org/10.1038/sj.leu.2404207.CrossRefPubMedGoogle Scholar
  176. 176.
    Okamoto K, Proia LA, Demarais PL. Disseminated cryptococcal disease in a patient with chronic lymphocytic leukemia on ibrutinib. Case Rep Infect Dis. 2016;2016:4642831.  https://doi.org/10.1155/2016/4642831.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Okuno SH, Frytak S. Mitomycin lung toxicity. Acute and chronic phases. Am J Clin Oncol. 1997;20(3):282–4.CrossRefGoogle Scholar
  178. 178.
    Onyx Pharmaceuticals Inc. Kyprolis (carfilzomib) [package insert]. Thousand Oaks; 2018.Google Scholar
  179. 179.
    Osawa M, Kudoh S, Sakai F, Endo M, Hamaguchi T, Ogino Y, Yoneoka M, Sakaguchi M, Nishimoto H, Gemma A. Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study. Int J Clin Oncol. 2015;20(6):1063–71.  https://doi.org/10.1007/s10147-015-0834-3.CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    OSI Pharmaceuticals L, an affiliate of Astellas Pharma US, Inc. Tarceva (erlotinib) [package insert]. Northbrook; 2016.Google Scholar
  181. 181.
    Otsuka America Pharmaceutical. Busulfan [package insert]. Rockville; 2015.Google Scholar
  182. 182.
    Ovation Pharmaceuticals. Cosmegen (dactinomycin) [package insert]. Deerfield; 2008.Google Scholar
  183. 183.
    Patel PN. Methylene blue for management of Ifosfamide-induced encephalopathy. Ann Pharmacother. 2006;40(2):299–303.  https://doi.org/10.1345/aph.1G114.CrossRefPubMedGoogle Scholar
  184. 184.
    Perez EA, Koehler M, Byrne J, Preston AJ, Rappold E, Ewer MS. Cardiac safety of lapatinib: pooled analysis of 3689 patients enrolled in clinical trials. Mayo Clin Proc. 2008;83(6):679–86.  https://doi.org/10.4065/83.6.679.CrossRefPubMedGoogle Scholar
  185. 185.
    Peroukides S, Makatsoris T, Koutras A, Tsamandas A, Onyenadum A, Labropoulou-Karatza C, Kalofonos H. Lapatinib-induced hepatitis: a case report. World J Gastroenterol. 2011;17(18):2349–52.  https://doi.org/10.3748/wjg.v17.i18.2349.CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Petri CR, O'Donnell PH, Cao H, Artz AS, Stock W, Wickrema A, Hard M, van Besien K. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant. Leuk Lymphoma. 2014;55(12):2866–73.  https://doi.org/10.3109/10428194.2014.897701.CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    Pfizer. Inlyta (axitinib) [package insert]. New York; 2014.Google Scholar
  188. 188.
    Pfizer. Navelbine (vinorelbine) [package insert]; Research Triangle Park; 2017a.Google Scholar
  189. 189.
    Pfizer. Sutent (sunitinib) [package insert]. New York; 2017b.Google Scholar
  190. 190.
    Pfizer Inc. Xalkori (crizotinib) [package insert]. New York; 2017.Google Scholar
  191. 191.
    Pfizer Labs. Ibrance (palbociclib) [package insert]. New York; 2017.Google Scholar
  192. 192.
    Pharmacia & Upjohn Camptosar (irinotecan) [package insert]. New York; 2016.Google Scholar
  193. 193.
    Pharmacyclics. Imbruvica (ibrutinib) [package insert]. Sunnyvale; 2017.Google Scholar
  194. 194.
    Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer. 2010;116(2):377–86.  https://doi.org/10.1002/cncr.24734.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Prasco Laboratories. Leukeran (chlorambucil) [package insert]. Mason; 2017.Google Scholar
  196. 196.
    Prometheus Laboratories Inc. Proleukin (aldesleukin) [prescribing information]. San Diego; 2012.Google Scholar
  197. 197.
    Qi WX, Fu S, Zhang Q, Guo XM. Bevacizumab increases the risk of severe congestive heart failure in cancer patients: an up-to-date meta-analysis with a focus on different subgroups. Clin Drug Investig. 2014;34(10):681–90.  https://doi.org/10.1007/s40261-014-0222-1.CrossRefPubMedGoogle Scholar
  198. 198.
    Quintas-Cardama A, Kantarjian H, Cortes J. Nilotinib-associated vascular events. Clin Lymphoma Myeloma Leuk. 2012;12(5):337–40.  https://doi.org/10.1016/j.clml.2012.04.005.CrossRefPubMedGoogle Scholar
  199. 199.
    Read WL, Mortimer JE, Picus J. Severe interstitial pneumonitis associated with docetaxel administration. Cancer. 2002;94(3):847–53.CrossRefGoogle Scholar
  200. 200.
    Robertson GL, Bhoopalam N, Zelkowitz LJ. Vincristine neurotoxicity and abnormal secretion of antidiuretic hormone. Arch Intern Med. 1973;132(5):717–20.CrossRefGoogle Scholar
  201. 201.
    Roboz GJ, Ritchie EK, Carlin RF, Samuel M, Gale L, Provenzano-Gober JL, Curcio TJ, Feldman EJ, Kligfield PD. Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide. J Clin Oncol. 2014;32(33):3723–8.  https://doi.org/10.1200/jco.2013.51.2913.CrossRefPubMedGoogle Scholar
  202. 202.
    Rosen AC, Balagula Y, Raisch DW, Garg V, Nardone B, Larsen N, Sorrell J, West DP, Anadkat MJ, Lacouture ME. Life-threatening dermatologic adverse events in oncology. Anti-Cancer Drugs. 2014;25(2):225–34.  https://doi.org/10.1097/cad.0000000000000032.CrossRefPubMedPubMedCentralGoogle Scholar
  203. 203.
    Rothenstein JM, Letarte N. Managing treatment-related adverse events associated with Alk inhibitors. Curr Oncol (Toronto, Ont). 2014;21(1):19–26.  https://doi.org/10.3747/co.21.1740.CrossRefGoogle Scholar
  204. 204.
    Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15(3):460–6.CrossRefGoogle Scholar
  205. 205.
    Sager PT, Balser B, Wolfson J, Nichols J, Pilot R, Jones S, Burris HA. Electrocardiographic effects of class 1 selective histone deacetylase inhibitor romidepsin. Cancer Med. 2015;4(8):1178–85.  https://doi.org/10.1002/cam4.467.CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Saif MW, McGee PJ. Hemolytic-uremic syndrome associated with gemcitabine: a case report and review of literature. J Pancreas. 2005;6(4):369–74.Google Scholar
  207. 207.
    Saif MW, Tomita M, Ledbetter L, Diasio RB. Capecitabine-related cardiotoxicity: recognition and management. J Support Oncol. 2008;6(1):41–8.PubMedGoogle Scholar
  208. 208.
    Salloum E, Khan KK, Cooper DL. Chlorambucil-induced seizures. Cancer. 1997;79(5):1009–13.CrossRefGoogle Scholar
  209. 209.
    Sankhalla KK, Chawla NS, Syed I, Chawla SP. Management of toxicities with pazopanib in advanced soft tissue sarcoma. Sarcoma Res Int. 2016;3(2):1032–8.Google Scholar
  210. 210.
    Sanofi-Aventis. Zaltrapt (afilibercept) [package insert]. Bridgewater; 2016.Google Scholar
  211. 211.
    Sanofi-Aventis LLC. Eloxatin (oxaliplatin) [package insert]. Bridgewater; 2015.Google Scholar
  212. 212.
    Sanofi-Aventis U.S. LLC. Taxotere (docetaxel) [package insert]. Bridgewater; 2015.Google Scholar
  213. 213.
    Sanofi-Aventis U.S. LLC. Jevtana (cabazitaxel) [package insert]. Bridgewater; 2017.Google Scholar
  214. 214.
    Sanofi Genzyme Corp. Caprelsa (vandetanib) [package insert]. Cambridge, MA; 2016.Google Scholar
  215. 215.
    Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123(18):2777–82.  https://doi.org/10.1182/blood-2013-10-512640.CrossRefPubMedGoogle Scholar
  216. 216.
    Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2008;26(32):5204–12.  https://doi.org/10.1200/jco.2007.15.6331.CrossRefPubMedGoogle Scholar
  217. 217.
    Seattle Genetics. Adcetris (brentuximab vedotin) [package insert]. Bothell; 2017.Google Scholar
  218. 218.
    Seet RC, Rabinstein AA. Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. QJM. 2012;105(1):69–75.  https://doi.org/10.1093/qjmed/hcr139.CrossRefPubMedGoogle Scholar
  219. 219.
    Serota DP, Mehta AK, Phadke VK. Invasive fungal sinusitis due to Mucor species in a patient on ibrutinib. Clin Infect Dis. 2017;  https://doi.org/10.1093/cid/cix1058.CrossRefGoogle Scholar
  220. 220.
    Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008;26(19):3204–12.  https://doi.org/10.1200/jco.2007.14.9260.CrossRefPubMedGoogle Scholar
  221. 221.
    Shank BR, Do B, Sevin A, Chen SE, Neelapu SS, Horowitz SB. Chimeric Antigen Receptor T Cells in Hematologic Malignancies. Pharmacotherapy. 2017;37(3):334–45.  https://doi.org/10.1002/phar.1900.CrossRefPubMedGoogle Scholar
  222. 222.
    Sharief U, Perry DJ. Delayed reversible posterior encephalopathy syndrome following chemotherapy with oxaliplatin. Clin Colorectal Cancer. 2009;8(3):163–5.  https://doi.org/10.3816/CCC.2009.n.026.CrossRefPubMedGoogle Scholar
  223. 223.
    Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O’Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Janne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94.  https://doi.org/10.1056/NEJMoa1214886.CrossRefPubMedGoogle Scholar
  224. 224.
    Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19(13):3244–54.  https://doi.org/10.1200/jco.2001.19.13.3244.CrossRefPubMedGoogle Scholar
  225. 225.
    Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875–84.  https://doi.org/10.1200/jco.2017.73.7585.CrossRefPubMedGoogle Scholar
  226. 226.
    Smith GA, Damon LE, Rugo HS, Ries CA, Linker CA. High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency. J Clin Oncol. 1997;15(2):833–9.  https://doi.org/10.1200/jco.1997.15.2.833.CrossRefPubMedGoogle Scholar
  227. 227.
    Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet (London, England). 2017;389(10072):917–29.  https://doi.org/10.1016/s0140-6736(17)30123-x.CrossRefGoogle Scholar
  228. 228.
    Spectrum Pharmaceuticals Beleodaq (belinostat) [package insert]. Irvine; 2017.Google Scholar
  229. 229.
    Steeghs N, de Jongh FE, Sillevis Smitt PA, van den Bent MJ. Cisplatin-induced encephalopathy and seizures. Anti-Cancer Drugs. 2003;14(6):443–6.  https://doi.org/10.1097/01.cad.0000078733.65608.38.CrossRefPubMedGoogle Scholar
  230. 230.
    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–31.  https://doi.org/10.1182/blood-2017-04-779405.CrossRefPubMedPubMedCentralGoogle Scholar
  231. 231.
    Stoica GS, Greenberg HE, Rossoff LJ. Corticosteroid responsive fludarabine pulmonary toxicity. Am J Clin Oncol. 2002;25(4):340–1.CrossRefGoogle Scholar
  232. 232.
    Stone RM, DeAngelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood. 2005;105(1):54–60.  https://doi.org/10.1182/blood-2004-03-0891.CrossRefPubMedGoogle Scholar
  233. 233.
    Sun Pharmaceutical Industries. Odomzo (sonidegib) [package insert]. Cranbury; 2017.Google Scholar
  234. 234.
    SuperGen. Mitozytrex (mitomycin) [package insert]. Dublin; 2002.Google Scholar
  235. 235.
    Swain SM, Ewer MS, Cortes J, Amadori D, Miles D, Knott A, Clark E, Benyunes MC, Ross G, Baselga J. Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in CLEOPATRA: a randomized, double-blind, placebo-controlled phase III study. Oncologist. 2013;18(3):257–64.  https://doi.org/10.1634/theoncologist.2012-0448.CrossRefPubMedPubMedCentralGoogle Scholar
  236. 236.
    Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol. 2002;47(5):672–84.CrossRefGoogle Scholar
  237. 237.
    Tesaro Inc. Zejula (niraparib) [package insert]. Waltham; 2017.Google Scholar
  238. 238.
    Teva Pharmaceuticals Inc. Adrucil (fluorouracil injection) [package insert]. North Wales; 2017.Google Scholar
  239. 239.
    Teva Pharmaceuticals USA Inc. Bendeka (bendamustine hydrochloride) [package insert]. North Wales; 2017.Google Scholar
  240. 240.
    Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Balint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16(7):763–74.  https://doi.org/10.1016/s1470-2045(15)00021-2.CrossRefPubMedGoogle Scholar
  241. 241.
    Thornburg A, Abonour R, Smith P, Knox K, Twigg HL 3rd. Hypersensitivity pneumonitis-like syndrome associated with the use of lenalidomide. Chest. 2007;131(5):1572–4.  https://doi.org/10.1378/chest.06-1734.CrossRefPubMedGoogle Scholar
  242. 242.
    Topp MS, Gokbuget N, Zugmaier G, Degenhard E, Goebeler ME, Klinger M, Neumann SA, Horst HA, Raff T, Viardot A, Stelljes M, Schaich M, Kohne-Volland R, Bruggemann M, Ottmann OG, Burmeister T, Baeuerle PA, Nagorsen D, Schmidt M, Einsele H, Riethmuller G, Kneba M, Hoelzer D, Kufer P, Bargou RC. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage all. Blood. 2012;120(26):5185–7.  https://doi.org/10.1182/blood-2012-07-441030.CrossRefPubMedGoogle Scholar
  243. 243.
    Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32(36):4134–40.  https://doi.org/10.1200/jco.2014.56.3247.CrossRefPubMedGoogle Scholar
  244. 244.
    Umemura S, Yamane H, Suwaki T, Katoh T, Yano T, Shiote Y, Takigawa N, Kiura K, Kamei H. Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer. J Cancer Res Clin Oncol. 2011;137(10):1469–75.  https://doi.org/10.1007/s00432-011-1013-1.CrossRefPubMedGoogle Scholar
  245. 245.
    United Therapeutics Corp. Unituxin (dinutuximab) [package insert]. Silver Spring; 2015.Google Scholar
  246. 246.
    Vahid B, Marik PE. Infiltrative lung diseases: complications of novel antineoplastic agents in patients with hematological malignancies. Can Respir J. 2008;15(4):211–6.CrossRefGoogle Scholar
  247. 247.
    Valent P, Hadzijusufovic E, Schernthaner GH, Wolf D, Rea D, le Coutre P. Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors. Blood. 2015;125(6):901–6.  https://doi.org/10.1182/blood-2014-09-594432.CrossRefPubMedGoogle Scholar
  248. 248.
    Verweij J, van Zanten T, Souren T, Golding R, Pinedo HM. Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis. Cancer. 1987;60(4):756–61.CrossRefGoogle Scholar
  249. 249.
    Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003;102(5):1578–82.  https://doi.org/10.1182/blood-2003-01-0255.CrossRefPubMedGoogle Scholar
  250. 250.
    Wanchoo R, Abudayyeh A, Doshi M, Edeani A, Glezerman IG, Monga D, Rosner M, Jhaveri KD. Renal toxicities of novel agents used for treatment of multiple myeloma. Clin J Am Soc Nephrol. 2017;12(1):176–89.  https://doi.org/10.2215/cjn.06100616.CrossRefPubMedGoogle Scholar
  251. 251.
    Wanchoo R, Jhaveri KD, Deray G, Launay-Vacher V. Renal effects of BRAF inhibitors: a systematic review by the cancer and the Kidney International Network. Clin Kidney J. 2016;9(2):245–51.  https://doi.org/10.1093/ckj/sfv149.CrossRefPubMedPubMedCentralGoogle Scholar
  252. 252.
    Waters MJ, Sukumaran S, Karapetis CS. Pemetrexed-Induced Interstitial pneumonitis: a case study and literature review. World J Oncol. 2014;5(5–6):232–6.  https://doi.org/10.14740/wjon845w.CrossRefPubMedPubMedCentralGoogle Scholar
  253. 253.
    Weiss RB, Poster DS, Penta JS. The nitrosoureas and pulmonary toxicity. Cancer Treat Rev. 1981;8(2):111–25.CrossRefGoogle Scholar
  254. 254.
    Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134–41.  https://doi.org/10.1200/jco.2011.35.5040.CrossRefPubMedGoogle Scholar
  255. 255.
    Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015;7(2):122–36.  https://doi.org/10.1177/1758834014566428.CrossRefPubMedPubMedCentralGoogle Scholar
  256. 256.
    Wenk KS, Pichard DC, Nasabzadeh T, Jang S, Venna SS. Vemurafenib-induced DRESS. JAMA Dermatol. 2013;149(10):1242–3.  https://doi.org/10.1001/jamadermatol.2013.5278.CrossRefPubMedGoogle Scholar
  257. 257.
    West-ward Pharmaceuticals. Thiotepa [package insert]. Eatontown; 2015.Google Scholar
  258. 258.
    Zamorano JL, Lancellotti P, Munoz DR, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GY, Lyon AR, Fernandez TL, Mohty D, Piepoli MF, Tamargo J, Torbicki A, Suter TM. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC committee for practice guidelines. Kardiol Pol. 2016;74(11):1193–233.  https://doi.org/10.5603/kp.2016.0156.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Melvin J. Rivera
    • 1
  • Bryan Do
    • 2
  • Jeffrey C. Bryan
    • 3
  • Terri Lynn Shigle
    • 4
  • Rina Patel
    • 5
    Email author
  1. 1.Clinical Pharmacy Specialist – Thoracic / Head and Neck MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Clinical Pharmacy Specialist – Lymphoma and MyelomaThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Clinical Pharmacy Specialist – LeukemiaThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Clinical Pharmacy Specialist – Stem Cell Transplantation and Cellular TherapyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Clinical Pharmacy Specialist – Critical Care / Nutrition SupportThe University of Texas MD Anderson Cancer CenterHoustonUSA

Section editors and affiliations

  • Todd W. Canada
    • 1
  • Jeffrey J. Bruno
    • 2
  1. 1.Clinical Pharmacy Svcs, Pharmacy Clinical ProgramsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Clinical Pharmacy Specialist – Critical Care / Nutrition SupportThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations