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

Neyssa Marina, Kay W. Chang, Marcio Malogolowkin, Wendy B. London, A. Lindsay Frazier, Richard B. Womer, Frederick Rescorla, Deborah F. Billmire, Mary M. Davis, Elizabeth J. Perlman, Roger Giller, Stephen J. Lauer, Thomas A. Olson

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. High-dose cisplatin combined with etoposide and bleomycin (HD-PEB) 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. METHODS. 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/m 2 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. 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.

Original languageEnglish (US)
Pages (from-to)841-847
Number of pages7
JournalCancer
Volume104
Issue number4
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

Fingerprint

Amifostine
Germ Cell and Embryonal Neoplasms
Etoposide
Cisplatin
Pediatrics
Bleomycin
Hearing
Disease-Free Survival
Yolk Sac
Residual Neoplasm
Vagina
indium-bleomycin
Neutropenia
Pelvis
Hearing Loss
Thrombocytopenia
Electrolytes
Neoplasm Metastasis
Carcinoma
Recurrence

Keywords

  • Bleomycin
  • Etoposide
  • High-dose cisplatin
  • Pediatric germ-cell tumors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Marina, Neyssa; Chang, Kay W.; Malogolowkin, Marcio; London, Wendy B.; Frazier, A. Lindsay; Womer, Richard B.; Rescorla, Frederick; Billmire, Deborah F.; Davis, Mary M.; Perlman, Elizabeth J.; Giller, Roger; Lauer, Stephen J.; Olson, Thomas A.

In: Cancer, Vol. 104, No. 4, 15.08.2005, p. 841-847.

Research output: Contribution to journalArticle

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 2005, '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, vol. 104, no. 4, pp. 841-847. https://doi.org/10.1002/cncr.21218
Marina, Neyssa ; Chang, Kay W. ; Malogolowkin, Marcio ; London, Wendy B. ; Frazier, A. Lindsay ; Womer, Richard B. ; Rescorla, Frederick ; Billmire, Deborah F. ; Davis, Mary M. ; Perlman, Elizabeth J. ; Giller, Roger ; Lauer, Stephen J. ; Olson, Thomas A. / 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. In: Cancer. 2005 ; Vol. 104, No. 4. pp. 841-847.
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abstract = "BACKGROUND. High-dose cisplatin combined with etoposide and bleomycin (HD-PEB) 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. METHODS. 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/m 2 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. 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.",
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T1 - Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors

T2 - A Children's Oncology Group study

AU - Marina, Neyssa

AU - Chang, Kay W.

AU - Malogolowkin, Marcio

AU - London, Wendy B.

AU - Frazier, A. Lindsay

AU - Womer, Richard B.

AU - Rescorla, Frederick

AU - Billmire, Deborah F.

AU - Davis, Mary M.

AU - Perlman, Elizabeth J.

AU - Giller, Roger

AU - Lauer, Stephen J.

AU - Olson, Thomas A.

PY - 2005/8/15

Y1 - 2005/8/15

N2 - BACKGROUND. High-dose cisplatin combined with etoposide and bleomycin (HD-PEB) 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. METHODS. 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/m 2 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. 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.

AB - BACKGROUND. High-dose cisplatin combined with etoposide and bleomycin (HD-PEB) 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. METHODS. 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/m 2 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. 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.

KW - Bleomycin

KW - Etoposide

KW - High-dose cisplatin

KW - Pediatric germ-cell tumors

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