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Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization

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Abstract

Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies.

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References

  1. Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T (1987) Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med 316:1622–1626. doi:10.1056/NEJM198706253162603

    Article  PubMed  CAS  Google Scholar 

  2. Vadas P, Gold M, Perelman B et al (2008) Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med 358:28–35. doi:10.1056/NEJMoa070030

    Article  PubMed  CAS  Google Scholar 

  3. Castells M (2006) Desensitization for drug allergy. Curr Opin Allergy Clin Immunol 6:476–481. doi:10.1097/ACI.0b013e3280108716

    Article  PubMed  CAS  Google Scholar 

  4. Castells MC, Tennant NM, Sloane DE et al (2008) Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 122:574–580. doi:10.1016/j.jaci.2008.02.044

    Article  PubMed  CAS  Google Scholar 

  5. Lee CW, Matulonis UA, Castells MC (2005) Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses. Gynecol Oncol 99:393–399. doi:10.1016/j.ygyno.2005.06.028

    Article  PubMed  Google Scholar 

  6. Lee CW, Matulonis UA, Castells MC (2004) Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions. Gynecol Oncol 95:370–376. doi:10.1016/j.ygyno.2004.08.002

    Article  PubMed  CAS  Google Scholar 

  7. Wu LC (2011) Immunoglobulin E receptor signaling and asthma. J Biol Chem 286:32891–32897. doi:10.1074/jbc.R110.205104

    Article  PubMed  CAS  Google Scholar 

  8. Kepley CL (2005) Antigen-induced reduction in mast cell and basophil functional responses due to reduced Syk protein levels. Int Arch Allergy Immunol 138:29–39. doi:10.1159/000087355

    Article  PubMed  CAS  Google Scholar 

  9. Shalit M, Levi-Schaffer F (1995) Challenge of mast cells with increasing amounts of antigen induces desensitization. Clin Exp Allergy 25:896–902

    Article  PubMed  CAS  Google Scholar 

  10. Sancho-Serra Mdel C, Simarro M, Castells M (2011) Rapid IgE desensitization is antigen specific and impairs early and late mast cell responses targeting FcepsilonRI internalization. Eur J Immunol 41:1004–1013. doi:10.1002/eji.201040810

    Article  PubMed  Google Scholar 

  11. Morales AR, Shah N, Castells M (2005) Antigen-IgE desensitization in signal transducer and activator of transcription 6-deficient mast cells by suboptimal doses of antigen. Ann Allergy Asthma Immunol 94:575–580. doi:10.1016/S1081-1206(10)61136-2

    Article  PubMed  CAS  Google Scholar 

  12. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD et al (1994) European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 12:2654–2666

    PubMed  CAS  Google Scholar 

  13. Kwon JS, Elit L, Finn M, Hirte H, Mazurka J, Moens F, Trim K (2002) A comparison of two prophylactic regimens for hypersensitivity reactions to paclitaxel. Gynecol Oncol 84:420–425. doi:10.1006/gyno.2001.6546

    Article  PubMed  CAS  Google Scholar 

  14. Markman M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J (2000) Paclitaxel-associated hypersensitivity reactions: experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center. J Clin Oncol 18:102–105

    PubMed  CAS  Google Scholar 

  15. Wiernik PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB, Paietta E (1987) Phase I clinical and pharmacokinetic study of taxol. Cancer Res 47:2486–2493

    PubMed  CAS  Google Scholar 

  16. Schrijvers D, Wanders J, Dirix L, Prove A, Vonck I, van Oosterom A, Kaye S (1993) Coping with toxicities of docetaxel (Taxotere). Ann Oncol 4:610–611

    PubMed  CAS  Google Scholar 

  17. Weiss RB, Donehower RC, Wiernik PH et al (1990) Hypersensitivity reactions from taxol. J Clin Oncol 8:1263–1268

    PubMed  CAS  Google Scholar 

  18. Price KS, Castells MC (2002) Taxol reactions. Allergy Asthma Proc 23:205–208

    PubMed  Google Scholar 

  19. Decorti G, Bartoli Klugmann F, Candussio L, Baldini L (1996) Effect of paclitaxel and Cremophor EL on mast cell histamine secretion and their interaction with adriamycin. Anticancer Res 16:317–320

    PubMed  CAS  Google Scholar 

  20. Eschalier A, Lavarenne J, Burtin C, Renoux M, Chapuy E, Rodriguez M (1988) Study of histamine release induced by acute administration of antitumor agents in dogs. Cancer Chemother Pharmacol 21:246–250

    Article  PubMed  CAS  Google Scholar 

  21. Essayan DM, Kagey-Sobotka A, Colarusso PJ, Lichtenstein LM, Ozols RF, King ED (1996) Successful parenteral desensitization to paclitaxel. J Allergy Clin Immunol 97:42–46

    Article  PubMed  CAS  Google Scholar 

  22. Szebeni J, Muggia FM, Alving CR (1998) Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst 90:300–306

    Article  PubMed  CAS  Google Scholar 

  23. Weiszhar Z, Czucz J, Revesz C, Rosivall L, Szebeni J, Rozsnyay Z (2012) Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20. Eur J Pharm Sci 45:492–498. doi:10.1016/j.ejps.2011.09.016

    Article  PubMed  CAS  Google Scholar 

  24. Feldweg AM, Lee CW, Matulonis UA, Castells M (2005) Rapid desensitization for hypersensitivity reactions to paclitaxel and docetaxel: a new standard protocol used in 77 successful treatments. Gynecol Oncol 96:824–829. doi:10.1016/j.ygyno.2004.11.043

    Article  PubMed  CAS  Google Scholar 

  25. Aabo K, Adams M, Adnitt P et al (1998) Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists’ Group. Br J Cancer 78:1479–1487

    Article  PubMed  CAS  Google Scholar 

  26. Gadducci A, Tana R, Teti G, Zanca G, Fanucchi A, Genazzani AR (2008) Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment for recurrent ovarian cancer. Int J Gynecol Cancer 18:615–620

    Article  PubMed  CAS  Google Scholar 

  27. Gomez R, Harter P, Luck HJ, Traut A, Kommoss S, Kandel M, du Bois A (2009) Carboplatin hypersensitivity: does introduction of skin test and desensitization reliably predict and avoid the problem? A prospective single-center study. Int J Gynecol Cancer 19:1284–1287. doi:10.1111/IGC.0b013e3181a418ff

    Article  PubMed  Google Scholar 

  28. Makrilia N, Syrigou E, Kaklamanos I, Manolopoulos L, Saif MW (2010) Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review. Met Based Drugs. doi: 10.1155/2010/207084

  29. Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, Belinson J (1999) Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 17:1141

    PubMed  CAS  Google Scholar 

  30. Maindrault-Goebel F, Andre T, Tournigand C, Louvet C, Perez-Staub N, Zeghib N, De Gramont A (2005) Allergic-type reactions to oxaliplatin: retrospective analysis of 42 patients. Eur J Cancer 41:2262–2267. doi:10.1016/j.ejca.2005.06.021

    Article  PubMed  CAS  Google Scholar 

  31. Polyzos A, Tsavaris N, Gogas H et al (2009) Clinical features of hypersensitivity reactions to oxaliplatin: a 10-year experience. Oncology 76:36–41. doi:10.1159/000178163

    Article  PubMed  CAS  Google Scholar 

  32. Sakaeda T, Kadoyama K, Yabuuchi H, Niijima S, Seki K, Shiraishi Y, Okuno Y (2011) Platinum agent-induced hypersensitivity reactions: data mining of the public version of the FDA adverse event reporting system, AERS. Int J Med Sci 8:332–338

    Article  PubMed  Google Scholar 

  33. Lee C, Gianos M, Klaustermeyer WB (2009) Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents. Ann Allergy Asthma Immunol 102: 179–187; quiz 87–89, 222. doi:10.1016/S1081-1206(10)60078-6

    Google Scholar 

  34. Schwartz JR, Bandera C, Bradley A, Brard L, Legare R, Granai CO, Dizon DS (2007) Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from Women and Infants’ Hospital. Gynecol Oncol 105:81–83. doi:10.1016/j.ygyno.2006.10.047

    Article  PubMed  CAS  Google Scholar 

  35. Hesterberg PE, Banerji A, Oren E, Penson RT, Krasner CN, Seiden MV, Wong JT (2009) Risk stratification for desensitization of patients with carboplatin hypersensitivity: clinical presentation and management. J Allergy Clin Immunol 123(1262–7):e1. doi:10.1016/j.jaci.2009.02.042

    PubMed  Google Scholar 

  36. Polyzos A, Tsavaris N, Kosmas C et al (2001) Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience. Oncology 61:129–133

    Article  PubMed  CAS  Google Scholar 

  37. Dizon DS, Sabbatini PJ, Aghajanian C, Hensley ML, Spriggs DR (2002) Analysis of patients with epithelial ovarian cancer or fallopian tube carcinoma retreated with cisplatin after the development of a carboplatin allergy. Gynecol Oncol 84:378–382. doi:10.1006/gyno.2001.6519

    Article  PubMed  CAS  Google Scholar 

  38. Chung CH, O’Neil BH (2009) Infusion reactions to monoclonal antibodies for solid tumors: immunologic mechanisms and risk factors. Oncology (Williston Park) 23:14–17

    Google Scholar 

  39. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ (2010) The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 9:325–338. doi:10.1038/nrd3003

    Article  PubMed  CAS  Google Scholar 

  40. Brennan PJ, Rodriguez Bouza T, Hsu FI, Sloane DE, Castells MC (2009) Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. J Allergy Clin Immunol 124:1259–1266. doi:10.1016/j.jaci.2009.09.009

    Article  PubMed  CAS  Google Scholar 

  41. Brown SG (2004) Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 114:371–376. doi:10.1016/j.jaci.2004.04.029

    Article  PubMed  Google Scholar 

  42. Legere HJ 3rd, Palis RI, Rodriguez Bouza T, Uluer AZ, Castells MC (2009) A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros 8:418–424. doi:10.1016/j.jcf.2009.08.002

    Article  PubMed  Google Scholar 

  43. Breslow RG, Caiado J, Castells MC (2009) Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desensitization. Ann Allergy Asthma Immunol 102:155–160. doi:10.1016/S1081-1206(10)60247-5

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women’s Hospital-Harvard Medical School, Smith Building, Room 626D, 1 Jimmy Fund Way, Boston, MA, 02115, USA

    Mariana Castells & Maria del Carmen Sancho-Serra

  2. Unidad de Investigación, Hospital Clinico Universitario de Valladolid, Valladolid, Spain

    Maria Simarro

  3. Departamento de Microbiología, Facultad de Medicina de Valladolid, Valladolid, Spain

    Maria Simarro

Authors
  1. Mariana Castells
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  2. Maria del Carmen Sancho-Serra
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  3. Maria Simarro
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Correspondence to Mariana Castells.

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This paper is part of the Symposium in Writing: AllergoOncology: The Role of Th2 responses in cancer.

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Castells, M., Sancho-Serra, M.d.C. & Simarro, M. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization. Cancer Immunol Immunother 61, 1575–1584 (2012). https://doi.org/10.1007/s00262-012-1273-x

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  • DOI: https://doi.org/10.1007/s00262-012-1273-x

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