A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

Ann Oncol. 2011 May;22(5):1054-1061. doi: 10.1093/annonc/mdq575. Epub 2010 Nov 8.

Abstract

Background: To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor-prognosis germ-cell cancer (GCC).

Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual.

Results: One hundred thirty-one patients were included in this analysis. The complete response rates in the HD-CT and in the BEP arm did not differ: (intention to treat) 44.6% versus 33.3% (P = 0.18). There was no difference in FFS between the two treatment arms (P = 0.057, 66 events). At 2 years, the FFS rate was 44.8% [95% confidence interval (CI) 32.5-56.4] and 58.2%, respectively (95% CI 48.0-71.9); but this 16.3% (standard deviation 7.5%) difference was not statistically significant (P = 0.060). Overall survival did not differ between the two groups (log-rank P > 0.1, 47 deaths).

Conclusion: This study could not demonstrate that high-dose chemotherapy given as part of first-line therapy improves outcome in patients with poor-prognosis GCC.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Chorionic Gonadotropin / blood
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Disease-Free Survival
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Humans
  • Ifosfamide / adverse effects
  • Ifosfamide / therapeutic use
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood
  • Male
  • Mediastinal Neoplasms / diagnosis
  • Mediastinal Neoplasms / mortality
  • Mediastinal Neoplasms / therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms, Germ Cell and Embryonal / diagnosis
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / therapy*
  • Prognosis
  • Retroperitoneal Neoplasms / diagnosis
  • Retroperitoneal Neoplasms / mortality
  • Retroperitoneal Neoplasms / therapy*
  • Stem Cell Transplantation*
  • Testicular Neoplasms / diagnosis
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / therapy*
  • Young Adult
  • alpha-Fetoproteins / metabolism

Substances

  • AFP protein, human
  • Biomarkers, Tumor
  • Chorionic Gonadotropin
  • alpha-Fetoproteins
  • Bleomycin
  • Etoposide
  • L-Lactate Dehydrogenase
  • Cisplatin
  • Ifosfamide

Supplementary concepts

  • BEP protocol