Equivalence of three or four cycles of bleomycin, etoposide, and cisplatinchemotherapy 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 medicalresearch council

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. Th e 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 1 00 mg/m(2) days 1 through 5 or 165 mg/m2 days 1 through 3, cisplatin 100 mg /m2, 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 cycle s 1 through 3. The randomization procedure allowed some investigators to pa rticipate only in the comparison of three versus four cycles. Results: From March 1995 until April 1998, 812 patients were randomly assig ned to receive three or four cycles: of these, 681 were also randomly assig ned to the 5-day or the 3-day schedule. Histology, marker values, and disea se extent are well balanced in the treatment arms of the two comparisons. T he 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% confidenc e limit [CL], -3.8%, +1.8%). Equivalence for three versus four cycles is ch imed 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, equiv alence is claimed in this comparison also. Frequencies of hematologic and n onhematologic toxicities were essentially similar. Quality of life was main tained better in patients receiving three cycles; no differences were defec ted between 3 and 5 days of treatment. Conclusion: We conclude that three cycles of BEP, with etoposide at 500 mg/ m2, is sufficient therapy in good-prognosis germ cell cancer and that the a dministration of the chemotherapy in 3 days has no detrimental effect on th e effectiveness of the BEP regimen. (C) 2001 by American Society of Clinica l Oncology.