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. Cancer 2005 Aug 15;104(4):841-7
Date
07/07/2005Pubmed ID
15999362DOI
10.1002/cncr.21218Scopus ID
2-s2.0-23444455599 (requires institutional sign-in at Scopus site) 92 CitationsAbstract
BACKGROUND: 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 decreased.
METHODS: Eligibility criteria included age < 15 years and unresectable Stage III/IV extracranial, extragonadal PGCT. Patients received bleomycin 15 IU/m(2) on Day 1, then etoposide 100 mg/m(2) per day, amifostine 825 mg/m(2) per day, and cisplatin 40 mg/m(2)per 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.
RESULTS: 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.
CONCLUSIONS: Amifostine did not protect against HDPEB-associated ototoxicity.
Author List
Marina N, Chang KW, Malogolowkin M, London WB, Frazier AL, Womer RB, Rescorla F, Billmire DF, Davis MM, Perlman EJ, Giller R, Lauer SJ, Olson TA, Children's Oncology GroupMESH terms used to index this publication - Major topics in bold
AdolescentAmifostine
Antineoplastic Combined Chemotherapy Protocols
Bleomycin
Child
Child, Preschool
Cisplatin
Etoposide
Female
Hearing Disorders
Humans
Infant
Male
Neoplasms, Germ Cell and Embryonal
Pilot Projects
Radiation-Protective Agents
