Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial

Cancer. 2003 Apr 15;97(8):1869-75. doi: 10.1002/cncr.11271.

Abstract

Background: Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system.

Methods: From October 1987 to April 1992, 304 patients with advanced-stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty-six patients were eligible and fully evaluable. With a median follow-up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression-free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms.

Results: With a longer follow-up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor-risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic toxicity, occurred on the VIP arm.

Conclusions: With a median follow-up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide-containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate-risk germ cell tumors, four cycles of BEP remain the standard therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use*
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use*
  • Etoposide / adverse effects
  • Etoposide / therapeutic use*
  • Follow-Up Studies
  • Germinoma / classification
  • Germinoma / drug therapy*
  • Germinoma / pathology
  • Humans
  • Ifosfamide / adverse effects
  • Ifosfamide / therapeutic use*
  • Male
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Bleomycin
  • Etoposide
  • Cisplatin
  • Ifosfamide

Supplementary concepts

  • BEP protocol
  • ICE protocol 1