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Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors†‡
A children's oncology group study
Article first published online: 5 JUL 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 4, pages 841–847, 15 August 2005
How to Cite
Marina, N., Chang, K. W., Malogolowkin, M., London, W. B., Frazier, A. L., Womer, R. B., Rescorla, F., Billmire, D. F., Davis, M. M., Perlman, E. J., Giller, R., Lauer, S. J. and Olson, T. A. (2005), Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors. Cancer, 104: 841–847. doi: 10.1002/cncr.21218
Presented, in part, at the American Society of Clinical Oncology, Chicago, Illinois, June 2003.
A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at http://www.childrensoncologygroup.org/admin/ grantinfo.htm.
- Issue published online: 2 AUG 2005
- Article first published online: 5 JUL 2005
- Manuscript Accepted: 6 APR 2005
- Manuscript Revised: 7 FEB 2005
- Manuscript Received: 29 NOV 2004
- pediatric germ-cell tumors;
- high-dose cisplatin;
High-dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event-free survival (EFS) in advanced pediatric germ-cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity deccreased.
Eligibility criteria included age < 15 years and unresectable Stage III/IV extracranial, extragonadal PGCT. Patients received bleomycin 15 IU/m2 on Day 1, then etoposide 100 mg/m2 per day, amifostine 825 mg/m2 per day, and cisplatin 40 mg/m2per day on Days 1–5, intravenously. The cycles were repeated every 3–4 weeks with imaging evaluation after 4 cycles. Patients with residual radiographic abnormalities underwent resection. Patients with residual tumor received two additional HDPEB cycles. Hearing evaluations were required at diagnosis and after two and four cycles. Audiologic results were reviewed and compared with historical controls treated with HDPEB.
Twenty-five eligible patients were enrolled between April 2000 and April 2002. Their median age was 1.6 years (range, 0.64–13.9 years), 17 patients were female, 11 had metastases, and 24 had a yolk sac carcinoma component histologically. Primary sites included sacrococcygeal area/pelvis (n = 15), vagina (n = 5), and other (n = 5). Two-year EFS and overall survival were 83.5% ± 12.8% and 85.6% ± 12.3%, respectively. Eight patients were removed from the study (four had progressive disease/disease recurrence and four had ototoxicity). Grade 3/4 toxicities included neutropenia (n = 20), thrombocytopenia (n = 14), electrolyte imbalances (n = 14), and gastrointestinal toxicity (n = 12). Twenty-four of 25 patients received hearing evaluations, and 75% had significant hearing loss.
Amifostine did not protect against HDPEB-associated ototoxicity. Cancer 2005. © 2005 American Cancer Society.