Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council.

Abstract

PURPOSE:

To test the equivalence of three versus four cycles of bleomycin, etoposide, and cisplatin (BEP) and of the 5-day schedule versus 3 days per cycle in good-prognosis germ cell cancer.

PATIENTS AND METHODS:

The study was designed as a 2 x 2 factorial trial. The aim was to rule out a 5% decrease in the 2-year progression-free survival (PFS) rate. The study included the assessment of patient quality of life. A cycle of BEP consisted of etoposide 500 mg/m(2), administered at either 100 mg/m(2) days 1 through 5 or 165 mg/m(2) days 1 through 3, cisplatin 100 mg/m(2), administered at either 20 mg/m(2) days 1 through 5 or 50 mg/m(2) days 1 and 2. Bleomycin 30 mg was administered on days 1, 8, and 15 during cycles 1 through 3. The randomization procedure allowed some investigators to participate only in the comparison of three versus four cycles.

RESULTS:

From March 1995 until April 1998, 812 patients were randomly assigned to receive three or four cycles: of these, 681 were also randomly assigned to the 5-day or the 3-day schedule. Histology, marker values, and disease extent are well balanced in the treatment arms of the two comparisons. The projected 2-year PFS is 90.4% on three cycles and 89.4% on four cycles. The difference in PFS between three and four cycles is -1.0% (80% confidence limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is claimed because both the upper and lower bounds of the 80% CL are less than 5%. In the 5- versus 3-day comparison, the projected 2-year PFS is 88.8% and 89.7%, respectively (difference, -0.9%, (80% CL, -4.1%, +2.2%). Hence, equivalence is claimed in this comparison also. Frequencies of hematologic and nonhematologic toxicities were essentially similar. Quality of life was maintained better in patients receiving three cycles; no differences were detected between 3 and 5 days of treatment.

CONCLUSION:

We conclude that three cycles of BEP, with etoposide at 500 mg/m(2), is sufficient therapy in good-prognosis germ cell cancer and that the administration of the chemotherapy in 3 days has no detrimental effect on the effectiveness of the BEP regimen.

• Authors: R de Wit, J T Roberts, P M Wilkinson, P H de Mulder, G M Mead, S D Fosså, P Cook, L de Prijck, S Stenning, L Collette
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 6 Pg. 1629-40 (Mar 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11250991 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bleomycin
• Etoposide
• Cisplatin

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Bleomycin (administration & dosage)
• Cisplatin (administration & dosage)
• Disease-Free Survival
• Drug Administration Schedule
• Etoposide (administration & dosage)
• Humans
• Male
• Middle Aged
• Neoplasms, Germ Cell and Embryonal (drug therapy, pathology)
• Prognosis
• Quality of Life
• Seminoma (drug therapy, pathology)
• Testicular Neoplasms (drug therapy, pathology)
• Treatment Outcome