Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882

Barbara Cushing, Roger Giller, John W. Cullen, Neyssa M. Marina, Stephen J. Lauer, Thomas A. Olson, Paul C. Rogers, Paul Colombani, Frederick Rescorla, Deborah F. Billmire, Charles D. Vinocur, Edith P. Hawkins, Mary Margaret Davis, Elizabeth J. Perlman, Wendy B. London, Robert P. Castleberry

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Purpose: To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods: Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results: One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion: Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.

Original languageEnglish (US)
Pages (from-to)2691-2700
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number13
DOIs
StatePublished - Dec 1 2004

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Germ Cell and Embryonal Neoplasms
Bleomycin
Etoposide
Combination Drug Therapy
Cisplatin
Pediatrics
Neoplasms
Poisons
Therapeutics
Drug Therapy
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors : A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882. / Cushing, Barbara; Giller, Roger; Cullen, John W.; Marina, Neyssa M.; Lauer, Stephen J.; Olson, Thomas A.; Rogers, Paul C.; Colombani, Paul; Rescorla, Frederick; Billmire, Deborah F.; Vinocur, Charles D.; Hawkins, Edith P.; Davis, Mary Margaret; Perlman, Elizabeth J.; London, Wendy B.; Castleberry, Robert P.

In: Journal of Clinical Oncology, Vol. 22, No. 13, 01.12.2004, p. 2691-2700.

Research output: Contribution to journalArticle

Cushing, Barbara ; Giller, Roger ; Cullen, John W. ; Marina, Neyssa M. ; Lauer, Stephen J. ; Olson, Thomas A. ; Rogers, Paul C. ; Colombani, Paul ; Rescorla, Frederick ; Billmire, Deborah F. ; Vinocur, Charles D. ; Hawkins, Edith P. ; Davis, Mary Margaret ; Perlman, Elizabeth J. ; London, Wendy B. ; Castleberry, Robert P. / Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors : A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 13. pp. 2691-2700.
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title = "Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882",
abstract = "Purpose: To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods: Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results: One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6{\%} ± 3.6{\%} v 80.5{\%} ± 4.8{\%} for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7{\%} ± 3.3{\%} v PEB 86.0{\%} ± 4.1{\%}). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion: Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.",
author = "Barbara Cushing and Roger Giller and Cullen, {John W.} and Marina, {Neyssa M.} and Lauer, {Stephen J.} and Olson, {Thomas A.} and Rogers, {Paul C.} and Paul Colombani and Frederick Rescorla and Billmire, {Deborah F.} and Vinocur, {Charles D.} and Hawkins, {Edith P.} and Davis, {Mary Margaret} and Perlman, {Elizabeth J.} and London, {Wendy B.} and Castleberry, {Robert P.}",
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T1 - Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors

T2 - A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882

AU - Cushing, Barbara

AU - Giller, Roger

AU - Cullen, John W.

AU - Marina, Neyssa M.

AU - Lauer, Stephen J.

AU - Olson, Thomas A.

AU - Rogers, Paul C.

AU - Colombani, Paul

AU - Rescorla, Frederick

AU - Billmire, Deborah F.

AU - Vinocur, Charles D.

AU - Hawkins, Edith P.

AU - Davis, Mary Margaret

AU - Perlman, Elizabeth J.

AU - London, Wendy B.

AU - Castleberry, Robert P.

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Purpose: To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods: Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results: One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion: Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.

AB - Purpose: To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity. Patients and Methods: Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m2 on day 1, etoposide 100 mg/m2 on days 1 through 5, and either high-dose cisplatin 40 mg/m2 on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m2 on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen. Results: One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate ± SE (89.6% ± 3.6% v 80.5% ± 4.8% for PEB; P = .0284). There was no significant difference in OS (HDPEB 91.7% ± 3.3% v PEB 86.0% ± 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB. Conclusion: Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.

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