Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial

Background Most patients with metastatic germ-cell tumours are cured with c hemotherapy. However, the optimum chemotherapy regimen is uncertain, and th ere is variation in international practice. We did a multicentre randomised trial to compare two standard chemotherapy regimens for men with good-prog nosis germ-cell tumours. Methods Good prognosis was defined by modified Memorial Sloan-Kettering cri teria. The first regimen (regimen A) was based on treatment recommendations from Indiana University and comprised three cycles of 20 mg/m(2) cisplatin on days 1-5, 100 mg/m(2) etoposide on days 1-5, and 30 kU bleomycin on day s 1, 8, and 15, repeated every 21 days. The second regimen (regimen B) was based on the control regimen of a published randomised clinical trial and c omprised four cycles of 100 mg/m(2) cisplatin on day 1, 120 mg/m(2) etoposi de on days 1-3, and 30 kU bleomycin on day 1, repeated every 21 days. The p rimary outcome measure was overall survival. Analysis was by intention to t reat. Findings 166 patients were randomised, 83 to each regimen. The trial was st opped when the second planned interim analysis met predefined stopping rule s. The median follow-up was 33 months, Overall survival was substantially b etter with regimen A (three vs 13 deaths, hazard ratio 0.22 [95% CI 0.06-0. 77], p=0.008). This difference was due to deaths from cancer tone vs nine), and not deaths from treatment (two vs two) and remained significant after adjustment for other prognostic factors (0.25 [0.07-0.88], p=0.03). Interpretation In men with good-prognosis germ-cell tumours, the regimen de veloped at Indiana University is superior to the alternative regimen studie d in this trial. The lower total dose and dose-intensity of bleomycin and t he lower dose-intensity of etoposide in regimen B could be responsible for the worse outcome.