Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: Updated analysis of a randomized trial

Background The Australian and New Zealand Germ Cell Trials Group conducted a multicenter randomized phase III trial in men with good-prognosis germ cell tumors of two standard chemotherapy regimens that contained bleomycin, etoposide, and cisplatin but differed in the scheduling and total dose of cisplatin, the total dose of bleomycin, and the scheduling and dose intensity of etoposide. The trial was stopped early at a median follow-up of 33 months after a planned interim analysis found a survival benefit for the more dose-intense regimen. The aim of this analysis was to determine if this survival benefit was maintained with long-term follow-up.MethodsBetween February 1994 and April 2000, 166 men with good-prognosis metastatic germ cell tumors defined by modified Memorial Sloan-Kettering criteria were randomly assigned to receive 3B90E500P (three cycles, repeated every 21 days, of 30 kU bleomycin on days 1, 8, and 15; 100 mg/m² etoposide on days 1-5; and 20 mg/m² cisplatin on days 1-5; n = 83) or 4B₃₀E₃₆₀P (four cycles, repeated every 21 days, of 30 kU bleomycin on day 1, 120 mg/m² etoposide on days 1-3, and 100 mg/m² cisplatin on day 1; n = 83). Endpoints included overall survival, progression-free survival, and quality of life and side effects, which were assessed using the Spitzer Quality of Life Index and the GLQ-8, respectively, before random assignment and during and after treatment. All analyses were by intention to treat. All P values are two-sided.ResultsThe median follow-up was 8.5 years. All but five survivors (3%) were followed up for at least 5 years. Overall survival remained better in those assigned to 3B₉₀E₅₀₀P than in those assigned to 4B₃₀E₃₆₀P (8-year survival: 92% vs 83%; hazard ratio of death = 0.38, 95% confidence interval = 0.15 to 0.97, P =. 037). Progression-free survival favored 3B₉₀E₅₀₀P but was not statistically significantly different between the treatment groups (8-year progression-free survival, 3B₉₀E₅₀₀P vs 4B ₃₀E₃₆₀P: 86% vs 79%; hazard ratio of progression = 0.6, 95% confidence interval = 0.3 to 1.1, P =. 15). At the end of treatment, average scores for most side effect scales favored 3B₉₀E₅₀₀P. After the completion of treatment, average GLQ-8 scores for numbness (P =. 003) and hair loss (P =. 04) and the Spitzer Quality of Life Index (P =. 05) favored 3B₉₀E₅₀₀P.ConclusionThe survival benefit of 3B ₉₀E₅₀₀P over 4B₃₀E₃₆₀P was maintained with long-term follow-up.