Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group

J Clin Oncol. 1997 May;15(5):1837-43. doi: 10.1200/JCO.1997.15.5.1837.

Abstract

Purpose: This prospective randomized trial was designed to compare the efficacy of etoposide plus cisplatin (EP) versus bleomycin, etoposide, and cisplatin (BEP) chemotherapy in patients with good-prognosis metastatic nonseminomatous testicular cancer.

Patients and methods: Four hundred nineteen patients with good-prognosis nonseminomatous testicular cancer were randomized to receive four cycles of cisplatin 20 mg/m2 on days 1 to 5 plus etoposide 120 mg/m2 on days 1, 3, and 5 with or without bleomycin 30 mg weekly.

Results: Of 395 eligible patients, 169 of 195 patients allocated to EP (87%) and 189 of 200 patients allocated to BEP (95%) achieved a complete response with chemotherapy alone or after postchemotherapy surgery. These results are significantly different (P = .0075). After a median follow-up duration of 7.3 years, eight patients (4%) on each treatment arm relapsed. In view of the low number of unfavorable treatment outcomes (11%), no significant differences were detected in time to progression (P = .136) and survival (P = .262). Both the acute and late pulmonary toxicity and neurotoxicity were significantly greater in patients who received BEP, whereas Raynaud's phenomenon occurred exclusively in patients who received BEP (P < .001). Two patients treated with BEP died of bleomycin pulmonary toxicity.

Conclusion: BEP is the most effective combination regimen in the treatment of disseminated nonseminomatous germ cell cancer. In this particular BEP regimen with etoposide at a dose of 360 mg/m2 per cycle, even in good-prognosis patients, bleomycin cannot be deleted without compromising treatment efficacy, but its use is associated with more toxicity (particularly pulmonary) and efforts to reduce this merit further exploration.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Combined Modality Therapy
  • Disease Progression
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Germinoma / drug therapy*
  • Germinoma / secondary
  • Germinoma / surgery
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / surgery

Substances

  • Bleomycin
  • Etoposide
  • Cisplatin

Supplementary concepts

  • BEP protocol
  • VP-P protocol