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Supportive Therapy and Toxicity

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Pediatric Liver Tumors

Part of the book series: Pediatric Oncology ((PEDIATRICO))

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Abstract

The treatment of primary liver cancers in children requires chemotherapy in addition to surgery for cure. The most effective chemotherapeutic agents remain cisplatin and doxorubicin both for hepatoblastoma and hepatocellular carcinoma. Unfortunately, both these drugs have short and long-term toxicities, although to a certain extent they can be ameliorated by reducing the cumulative dose and changing the method of administration. This chapter considers the improvements in supportive care of children receiving chemotherapy, and also discusses the late effects of therapy. In the case of cisplatin, the late effects to the kidney and the ear can be detected early within 1 to 2 years of ending treatment. After this time, very little or no improvement can be expected. However, with anthracycline treatment, the cardiotoxic effects are progressive and may take 20–30 years to develop. Long-term follow-up into adult life with 5 yearly echocardiographic screening is advised.

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References

  • Allen GC, Tiu C, Koike K, Ritchey AK, Kurs-Lasky M, Wax MK (1998) Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy. Otolaryngol Head Neck Surg 118(5):584–588

    CAS  PubMed  Google Scholar 

  • Alvarez O, Freeman A, Bedros A, Call SK, Volsch J, Kalbermatter O, Halverson J, Convy L, Cook L, Mick K et al (1995) Randomized double-blind crossover ondansetron–dexamethasone versus ondansetron-placebo study for the treatment of chemotherapy-induced nausea and vomiting in pediatric patients with malignancies. J Pediatr Hematol Oncol 17(2):145–150

    Article  CAS  PubMed  Google Scholar 

  • Billingham ME, Masek MA (1993) The pathology of anthracycline cardiotoxicity in children, adolescents and adults. In: Bricker JT, Green DM, D’Angio GJ (eds) Cardiac toxicity after anthracycline treatment for childhood cancer. Wiley-Liss, New York, pp 17–24

    Google Scholar 

  • Blyth CC, Chen SC, Slavin MA, Serena C, Nguyen Q, Marriott D, Ellis D, Meyer W, Sorrell TC, Australian Candidemia Study (2009) Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Pediatrics 123(5):1360–1368

    Article  PubMed  Google Scholar 

  • Brock P, Bellman S (1991) Ototoxicity of cisplatinum. Br J Cancer 63(1):159–160

    Article  CAS  PubMed  Google Scholar 

  • Brock PR, Koliouskas DE, Barratt TM, Yeomans E, Pritchard J (1991a) Partial reversibility of cisplatin nephrotoxicity in children. J Pediatr 118(4 (Pt 1)):531–534

    CAS  PubMed  Google Scholar 

  • Brock PR, Bellman SC, Yeomans EC et al (1991b) Cisplatin ototoxicity in children: a practical grading system. Med Pediatr Oncol 19:295–300

    Article  CAS  PubMed  Google Scholar 

  • Brock PR, Yeomans EC, Bellman SC, Pritchard J (1992) Cisplatin therapy in infants: short and long-term morbidity. Br J Cancer Suppl 18:S36–S40

    CAS  PubMed  Google Scholar 

  • Brock P, Brichard B, Rechnitzer C, Langeveld NE, Lanning M, Söderhäll S, Laurent C (1996) An increased loading dose of ondansetron: a north european, double-blind randomised study in children, comparing 5 mg/m2 with 10 mg/m2. Eur J Cancer 32A(10):1744–1748

    Article  CAS  PubMed  Google Scholar 

  • Bryant J, Picot J, Levitt G, Sullivan I, Baxter L, Clegg A (2007) Clinical and cost effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer: a systematic review. Br J Cancer 96(2):226–230

    Article  CAS  PubMed  Google Scholar 

  • Children’s Oncology Group (2004) Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. www.survivorshipguidelines.org

  • Coradini PP, Cigana L, Selistre SG, Rosito LS, Brunetto AL (2007) Ototoxicity from cisplatin therapy in childhood ­cancer. J Pediatr Hematol Oncol 29(6):355–360

    Article  CAS  PubMed  Google Scholar 

  • Corbally MT (1993) Supportive care of the paediatric cancer patient. Semin Surg Oncol 9(6):461–466

    Article  CAS  PubMed  Google Scholar 

  • de Koning BA, van der Schoor SR, Wattimena DL, de Laat PC, Pieters R, van Goudoever JB (2007) Chemotherapy does not influence intestinal amino acid uptake in children. Pediatr Res 62(2):195–199

    Article  PubMed  Google Scholar 

  • Dhooge I, Dhooge C, Geukens S, De Clerck B, De Vel E, Vinck BM (2006) Distortion product otoacoustic emissions: an objective technique for the screening of hearing loss in children treated with platin derivatives. Int J Audiol 45(6):337–343

    Article  PubMed  Google Scholar 

  • Dupuis LL, Nathan PC (2010) Optimizing emetic control in children receiving antineoplastic therapy: beyond the guidelines. Paediatr Drugs 12(1):51–61

    Article  PubMed  Google Scholar 

  • Gilmer Knight KR, Kraemer DF, Neuwelt EA (2005) Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may impact academic and social development. SIOPEL Publ JCO 23(34):8588–8596

    Article  Google Scholar 

  • Hanigan MH, Devarajan P (2003) Cisplatin nephrotoxicity: molecular mechanisms. Cancer Ther 1:47–61

    PubMed  Google Scholar 

  • Härtel C, Deuster M, Lehrnbecher T, Schultz C (2007) Current approaches for risk stratification of infectious complications in pediatric oncology. Pediatr Blood Cancer 49(6):767–773, Review

    Article  PubMed  Google Scholar 

  • Hasler WL (1999) Serotonin receptor physiology: relation to emesis. Dig Dis Sci 44(8 Suppl):108S–113S, Review

    CAS  PubMed  Google Scholar 

  • Helt-Cameron J, Allen PJ (2009) Cisplatin ototoxicity in children: implications for primary care providers. Pediatr Nurs 35(2):121–127, Review

    PubMed  Google Scholar 

  • Hewitt M, McQuade B, Stevens R (1993) The efficacy and safety of ondansetron in the prophylaxis of cancer-chemotherapy induced nausea and vomiting in children. Clin Oncol (R Coll Radiol) 5(1):11–14

    CAS  Google Scholar 

  • Hockenberry MJ, Schultz WH, Bennett B, Bryant R, Falletta JM (1989) Experience with minimal complications in implanted catheters in children. Am J Pediatr Hematol Oncol 11(3):295–299

    CAS  PubMed  Google Scholar 

  • Ilveskoski I, Saarinen UM, Wiklund T, Perkkio M et al (1998) Ototoxicity in children with malignant brain tumors treated with the “8 in 1” chemotherapy protocol. Med Pediatr Oncol 27:26–31

    Article  Google Scholar 

  • Ishizawa T, Hasegawa K, Tsuno NH, Tanaka M, Mise Y, Aoki T, Imamura H, Beck Y, Sugawara Y, Makuuchi M, Takahashi K, Kokudo N (2009) Predeposit autologous plasma donation in liver resection for hepatocellular carcinoma: toward ­allogenic blood-free operations. J Am Coll Surg 209(2):206–214, Epub 2009 May 1

    Article  PubMed  Google Scholar 

  • Israëls T, van de Wetering MD, Hesseling P, van Geloven N, Caron HN, Molyneux EM (2009a) Malnutrition and neutropenia in children treated for Burkitt lymphoma in Malawi. Pediatr Blood Cancer 53(1):47–52

    Article  PubMed  Google Scholar 

  • Israëls T, Borgstein E, Jamali M, de Kraker J, Caron HN, Molyneux EM (2009b) Acute malnutrition is common in Malawian patients with a Wilms tumour: a role for peanut butter. Pediatr Blood Cancer 53(7):1221–1226

    Article  PubMed  Google Scholar 

  • Katzenstein HM, Chang KW, Krailo M, Chen Z, Finegold MJ, Rowland J, Reynolds M, Pappo A, London WB, Malogolowkin M, Children’s Oncology Group (2009) Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma: a report of the Intergroup Hepatoblastoma Study P9645 as a part of the Children’s Oncology Group. Cancer 115(24):5828–5835

    Article  CAS  PubMed  Google Scholar 

  • Khan RB (2002) Migraine-type headaches in children receiving chemotherapy and ondansetron. J Child Neurol 17(11):857–858

    Article  PubMed  Google Scholar 

  • Knight KR, Kraemer DF, Winter C, Neuwelt EA (2007) Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol 25(10):1190–1195

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi R, Kaneda M, Sato T, Ichikawa M, Suzuki D, Ariga T (2008) The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: a 10-year analysis at a single institution at Japan. J Pediatr Hematol Oncol 30(12):886–890

    Article  PubMed  Google Scholar 

  • Kremer LC, van Dalen EC, Offringa M, Voûte PA (2002a) Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Ann Oncol 13(4):503–512, Review

    Article  CAS  PubMed  Google Scholar 

  • Kremer LC, van der Pal HJ, Offringa M, van Dalen EC, Voute PA (2002b) Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 13(6):819–829

    Article  CAS  PubMed  Google Scholar 

  • Kushner BH, Budnick A, Kramer K, Modak S, Cheung NK (2006) Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma. Cancer 107(2):417–422

    Article  CAS  PubMed  Google Scholar 

  • Levitt G, Anazodo A, Burch M, Bunch K (2009) Cardiac or cardiopulmonary transplantation in childhood cancer survivors: an increasing need? Eur J Cancer 45(17):3027–3034

    Article  PubMed  Google Scholar 

  • Li Y, Womer RB, Silber JH (2004) Predicting ototoxicity in children: influence of age and the cumulative dose. Eur J Cancer 40(16):2445–2451

    Article  CAS  PubMed  Google Scholar 

  • Lipshultz SE, Lipsitz SR, Mone SM et al (1995) Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 332:1738–1743

    Article  CAS  PubMed  Google Scholar 

  • Lipshultz SE, Lipsitz SR, Orav EJ (2007) Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin’s disease: a claim without compelling evidence. J Clin Oncol 25(21):3179, Author reply 3180

    Article  PubMed  Google Scholar 

  • Meckler G, Lindemulder S (2009) Fever and neutropenia in pediatric patients with cancer. Emerg Med Clin North Am 27(3):525–544

    Article  PubMed  Google Scholar 

  • Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, Robison LL, Yasui Y (2008) Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst 100(19):1368–1379

    Article  PubMed  Google Scholar 

  • Moore A, Pinkerton R (2009) Vincristine: can its therapeutic index be enhanced? Pediatr Blood Cancer 53(7):1180–1187, Review

    Article  PubMed  Google Scholar 

  • Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM (2009) Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339:b4606

    Article  PubMed  Google Scholar 

  • Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2003) Myocyte death, growth, and regeneration in cardiac hypertrophy and failure. Circ Res 92(2):139–150

    Article  CAS  PubMed  Google Scholar 

  • Nathan M, Selwood K, Clinical Practice Group of the RCN Paediatric Oncology Nurses Forum (2006) The use of blood products in paediatric oncology units in the UK. Paediatr Nurs 18(7):14–17

    PubMed  Google Scholar 

  • Pein F, Sakiroglu O, Dahan M et al (2004) Cardiac abnormalities 15 years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Instit Gustave Roussy. Br J Cancer 91:37–44

    Article  CAS  PubMed  Google Scholar 

  • Pereira CA, Petrilli AS, Carlesse FA, Luisi FA, da Silva KV, de Martino Lee ML (2009) Cefepime monotherapy is as effective as ceftriaxone plus amikacin in pediatric patients with cancer and high-risk febrile neutropenia in a randomized comparison. J Microbiol Immunol Infect 42(2):141–147

    CAS  PubMed  Google Scholar 

  • Perilongo G, Maibach R, Shafford E, Brugieres L, Brock P, Morland B, de Camargo B, Zsiros J, Roebuck D, Zimmermann A, Aronson D, Childs M, Widing E, Laithier V, Plaschkes J, Pritchard J, Scopinaro M, MacKinlay G, Czauderna P (2009) Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 361(17):1662–1670

    Article  CAS  PubMed  Google Scholar 

  • Rude RK, Singer FR, Gruber HE (2009) Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr 28(2):131–141, Review

    CAS  PubMed  Google Scholar 

  • Salzer WL, Devidas M, Carroll WL et al (2010) Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia. 1984–2001: A report from the children’s oncology group leukemia 24:355–370

    Article  CAS  PubMed  Google Scholar 

  • Seguy D, Berthon C, Micol JB, Darré S, Dalle JH, Neuville S, Bauters F, Jouet JP, Yakoub Agha I (2006) Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning. Transplantation 82(6):835–839

    Article  PubMed  Google Scholar 

  • SIGN (2004) Long term follow up of survivors of childhood cancer. A national clinical guideline. www.sign.ac.uk/pdf/sign76.pdf

  • Silber JH, Jakacki RI, Larsen RL, Goldwein JW, Barber G (1993) Increased risk of cardiac dysfunction after anthracyclines in girls. Med Pediatr Oncol 21:477–479

    Article  CAS  PubMed  Google Scholar 

  • Skinner R, Levitt G, Wallace WH (2005) Therapy based LTFU Practice Statement UKCCSG. www.ukccsg.org.uk/public/followup

  • Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID (2003) Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer 97:1991–1998

    Article  CAS  PubMed  Google Scholar 

  • Stockhorst U, Spennes-Saleh S, Körholz D, Göbel U, Schneider ME, Steingrüber HJ, Klosterhalfen S (2000) Anticipatory symptoms and anticipatory immune responses in pediatric cancer patients receiving chemotherapy: features of a classically conditioned response? Brain Behav Immun 14(3):198–218

    Article  CAS  PubMed  Google Scholar 

  • Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, Mendenhall NP, Sposto R, Chauvenet A, Schwartz CL (2007) Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other ­secondary malignancies in pediatric Hodgkin’s disease. J Clin Oncol 25(5):493–500

    Article  CAS  PubMed  Google Scholar 

  • Tukenova M, Guibout C, Oberlin O et al (2009) Long-term overall and cardiovascular mortality following childhood cancer: the role of cancer treatment. BMJ 339:b4691

    Article  Google Scholar 

  • van Dalen EC, van der Pal HJ, van den Bos C, Kok WE, Caron HN, Kremer LC (2006) Clinical heart failure during pregnancy and delivery in a cohort of female childhood cancer survivors treated with anthracyclines. Eur J Cancer 42(15):2549–2553

    Article  PubMed  Google Scholar 

  • van Dalen EC, Caron HN, Dickinson HO, Kremer LC (2008) Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev 2:CD003917

    PubMed  Google Scholar 

  • van Dalen EC, van der Pal HJ, Caron HN, Kremer LC (2009) Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev 4:CD005008

    PubMed  Google Scholar 

  • Von Hoff DD, Layard MW, Basa P et al (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717

    Google Scholar 

  • Zorowka PG, Schmitt HJ, Gutjahr P (1993) Evoked otoacoustic emissions and pure tone threshold audiometry in patients receiving cisplatinum therapy. Int J Pediatr Otorhinolaryngol 25(1–3):73–80

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dept. Paediatric Oncology, Great Ormond Street Hospital, NHS Trust & Institute of Child Health, Great Ormond Street, WC1N 3JH, London, United Kingdom

    Penelope Brock & Gill Levitt

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  1. Penelope Brock
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  2. Gill Levitt
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Correspondence to Penelope Brock .

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Editors and Affiliations

  1. Inst. Pathologie, Universität Bern, Murtenstr. 31, Bern, 3010, Switzerland

    Arthur Zimmermann

  2. Dipto. Pediatria, Unità di Oncoematologia Pediatrica, Università di Padova, Via Giustiniani 3, Padova, 35128, Italy

    Giorgio Perilongo

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Brock, P., Levitt, G. (2011). Supportive Therapy and Toxicity. In: Zimmermann, A., Perilongo, G. (eds) Pediatric Liver Tumors. Pediatric Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14504-9_15

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  • DOI: https://doi.org/10.1007/978-3-642-14504-9_15

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