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Current Oncology Reports
Published in: Current Oncology Reports 6/2010

01-11-2010

Can Anthracycline Therapy for Pediatric Malignancies Be Less Cardiotoxic?

Authors: Joy M. Fulbright, Winston Huh, Pete Anderson, Joya Chandra

Published in: Current Oncology Reports | Issue 6/2010

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Abstract

Anthracyclines have a central role in the treatment of cancer in pediatric patients but confer an increased risk of cardiac dysfunction. Several strategies have been employed to help reduce anthracycline-induced cardiotoxicity, including pretreating the patient with the iron chelator dexrazoxane and infusing the dose of anthracycline over a longer period. Much focus has also been placed on the development of methods that decrease the toxicity of parent compounds, specifically through the use of drug carriers such as liposomes, and on the development of new, potentially less toxic anthracycline derivatives, such as amrubicin and pixantrone. We provide a review of these strategies, focusing on studies in pediatric patients when available, and support the idea that anthracycline therapy can be less cardiotoxic in pediatric patients.
Literature
1.
Minotti G, Menna P, Salvatorelli E, et al.: Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004, 56:185–229.CrossRefPubMed
2.
Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA: A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973, 32:302–314.CrossRefPubMed
3.
Von Hoff DD, Rozencweig M, Layard M, et al.: Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med 1977, 62:200–208.CrossRef
4.
Anderson B: Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients. Pediatr Blood Cancer 2005, 44:584–588.CrossRefPubMed
5.
• Barry EV, Vrooman LM, Dahlberg SE, et al.: Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J Clin Oncol 2008, 26:1106–1111. The concern over the increased risk of secondary malignancies is a reason some clinicians are reluctant to use dexrazoxane. The authors dispute this concern by demonstrating in a study of 205 children dexrazoxane does not increase the risk of secondary malignancies (P = 0.66).CrossRefPubMed
6.
Schuchter LM, Hensley ML, Meropol NJ, Winer EP: 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2002, 20:2895–2903.CrossRefPubMed
7.
•• van Dalen EC, Caron HN, Dickinson HO, Kremer LC: Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database Syst Rev 2008, CD003917. This systematic review evaluates the data regarding cardioprotective agents, including an in-depth review of the literature regarding dexrazoxane’s use including the incidence of heart failure, side effects, response rates, and survival in patients pretreated with dexrazoxane prior to doxorubicin therapy versus those who were not.
8.
Silverman LB, Stevenson KE, O’Brien JE, et al.: Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985–2000). Leukemia 2010, 24:320–334.CrossRefPubMed
9.
Tebbi CK, London WB, Friedman D, et al.: Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. J Clin Oncol 2007, 25:493–500.CrossRefPubMed
10.
Hellmann K: Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin’s disease: a claim without evidence. J Clin Oncol 2007, 25:4689–4690; author reply 4690–4691.CrossRefPubMed
11.
Lipshultz SE, Lipsitz SR, Orav EJ: Dexrazoxane-associated risk for secondary malignancies in pediatric Hodgkin’s disease: a claim without compelling evidence. J Clin Oncol 2007, 25:3179; author reply 3180.CrossRefPubMed
12.
Cvetkovic RS, Scott LJ: Dexrazoxane: a review of its use for cardioprotection during anthracycline chemotherapy. Drugs 2005, 65:1005–1024.CrossRefPubMed
13.
•• van Dalen EC, van der Pal HJ, Caron HN, Kremer LC: Different dosage schedules for reducing cardiotoxicity in cancer patients receiving anthracycline chemotherapy. Cochrane Database Syst Rev 2009, CD005008. This is an in-depth systematic review of the literature regarding different dosing schedules of anthracyclines, including bolus versus prolonged infusion time.
14.
Escherich G, Gobel U, Jorch N, et al.: Daunorubicin-induced cell kill with 1-hour versus 24-hour infusions: a randomized comparison in children with newly diagnosed acute lymphoblastic leukemia. Klin Padiatr 2007, 219:134–138.CrossRefPubMed
15.
Lipshultz SE, Giantris AL, Lipsitz SR, et al.: Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol. J Clin Oncol 2002, 20:1677–1682.CrossRefPubMed
16.
Steinherz PG, Redner A, Steinherz L, et al.: Development of a new intensive therapy for acute lymphoblastic leukemia in children at increased risk of early relapse. The Memorial Sloan-Kettering-New York-II protocol. Cancer 1993, 72:3120–3130.CrossRefPubMed
17.
Gabizon A, Shmeeda H, Barenholz Y: Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet 2003, 42:419–436.CrossRefPubMed
18.
Colbern GT HA, Musterer RS: Significant increase in antitumor potency of doxorubicin HCL by its encapsulation in pegylated liposomes. J Liposome Res 1999, 9.
19.
Working PK, Newman MS, Sullivan T, Yarrington J: Reduction of the cardiotoxicity of doxorubicin in rabbits and dogs by encapsulation in long-circulating, pegylated liposomes. J Pharmacol Exp Ther 1999, 289:1128–1133.PubMed
20.
O’Brien ME, Wigler N, Inbar M, et al.: Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004, 15:440–449.CrossRefPubMed
21.
van Dalen EC, Michiels EM, Caron HN, Kremer LC: Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database Syst Rev 2006, CD005006.
22.
Batist G, Ramakrishnan G, Rao CS, et al.: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 2001, 19:1444–1454.PubMed
23.
Harris L, Batist G, Belt R, et al.: Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 2002, 94:25–36.CrossRefPubMed
24.
Sparano JA, Makhson AN, Semiglazov VF, et al.: Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol 2009, 27:4522–4529.CrossRefPubMed
25.
Marina NM, Cochrane D, Harney E, et al.: Dose escalation and pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in children with solid tumors: a pediatric oncology group study. Clin Cancer Res 2002, 8:413–418.PubMed
26.
Munoz A, Maldonado M, Pardo N, et al.: Pegylated liposomal doxorubicin hydrochloride (PLD) for advanced sarcomas in children: preliminary results. Pediatr Blood Cancer 2004, 43:152–155.CrossRefPubMed
27.
Bonadonna G, Gianni L, Santoro A, et al.: Drugs ten years later: epirubicin. Ann Oncol 1993, 4:359–369.PubMed
28.
Stohr W, Paulides M, Brecht I, et al.: Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study (CWS). J Cancer Res Clin Oncol 2006, 132:35–40.CrossRefPubMed
29.
Jain KK, Casper ES, Geller NL, et al.: A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer. J Clin Oncol 1985, 3:818–826.PubMed
30.
Buckley MM, Lamb HM: Oral idarubicin. A review of its pharmacological properties and clinical efficacy in the treatment of haematological malignancies and advanced breast cancer. Drugs Aging 1997, 11:61–86.CrossRefPubMed
31.
Vogler WR, Velez-Garcia E, Weiner RS, et al.: A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. J Clin Oncol 1992, 10:1103–1111.PubMed
32.
Berman E, Heller G, Santorsa J, et al.: Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood 1991, 77:1666–1674.PubMed
33.
O’Brien TA, Russell SJ, Vowels MR, et al.: Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children’s Cancer Study Group. Blood 2002, 100:2708–2716.CrossRefPubMed
34.
Thomas X, Archimbaud E: Mitoxantrone in the treatment of acute myelogenous leukemia: a review. Hematol Cell Ther 1997, 39:63–74.CrossRefPubMed
35.
Wells RJ, Adams MT, Alonzo TA, et al.: Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children’s Cancer Group Study 2951. J Clin Oncol 2003, 21:2940–2947.CrossRefPubMed
36.
Gibson BE, Wheatley K, Hann IM, et al.: Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials. Leukemia 2005, 19:2130–2138.CrossRefPubMed
37.
van Dalen EC, van der Pal HJ, Bakker PJ, et al.: Cumulative incidence and risk factors of mitoxantrone-induced cardiotoxicity in children: a systematic review. Eur J Cancer 2004, 40:643–652.PubMed
38.
Morisada S, Yanagi Y, Noguchi T, et al.: Antitumor activities of a novel 9-aminoanthracycline (SM-5887) against mouse experimental tumors and human tumor xenografts. Jpn J Cancer Res 1989, 80:69–76.PubMed
39.
Yamaoka T, Hanada M, Ichii S, et al.: Cytotoxicity of amrubicin, a novel 9-aminoanthracycline, and its active metabolite amrubicinol on human tumor cells. Jpn J Cancer Res 1998, 89:1067–1073.PubMed
40.
Noda T, Watanabe T, Kohda A, et al.: Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs. Invest New Drugs 1998, 16:121–128.CrossRefPubMed
41.
Suzuki T, Minamide S, Iwasaki T, et al.: Cardiotoxicity of a new anthracycline derivative (SM-5887) following intravenous administration to rabbits: comparative study with doxorubicin. Invest New Drugs 1997, 15:219–225.CrossRefPubMed
42.
Onoda S, Masuda N, Seto T, et al.: Phase II trial of amrubicin for treatment of refractory or relapsed small-cell lung cancer: Thoracic Oncology Research Group Study 0301. J Clin Oncol 2006, 24:5448–5453.CrossRefPubMed
43.
Takeda K, Takifuji N, Negoro S, et al.: Phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group (WJTOG) study. Invest New Drugs 2007, 25:377–383.CrossRefPubMed
44.
Yana T, Negoro S, Takada M, et al.: Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study. Invest New Drugs 2007, 25:253–258.CrossRefPubMed
45.
Akutsu M, Kano Y, Ogawa M, et al.: Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma. Gan To Kagaku Ryoho 2001, 28:1867–1876.PubMed
46.
Masaoka T, Ogawa M, Inoue K, et al.: Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma. Gan To Kagaku Ryoho 2001, 28:1857–1865.PubMed
47.
Denny WA, Wakelin LP: Kinetics of the binding of mitoxantrone, ametantrone and analogues to DNA: relationship with binding mode and anti-tumour activity. Anticancer Drug Des 1990, 5:189–200.PubMed
48.
El-Helw LM, Hancock BW: Pixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin’s lymphomas. Expert Opin Investig Drugs 2007, 16:1683–1691.CrossRefPubMed
49.
• Kavey RE, Allada V, Daniels SR, et al.: Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research. J Cardiovasc Nurs 2007, 22:218–253. Included in this statement are guidelines as to when to screen children for elevated cholesterol, along with when and how to treat elevated cholesterol.PubMed
Metadata
Title
Can Anthracycline Therapy for Pediatric Malignancies Be Less Cardiotoxic?
Authors
Joy M. Fulbright
Winston Huh
Pete Anderson
Joya Chandra
Publication date
01-11-2010
Publisher
Current Science Inc.
Published in
Current Oncology Reports / Issue 6/2010
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-010-0129-9

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