A Medical Research Council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma

The UK Medical Research Council conducted this trial of carboplatin chemoth erapy in advanced seminoma to compare single agent carboplatin with a stand ard combination of etoposide with cisplatin. The use of single agent carbop latin was expected to be associated with reduced toxicity. A total of 130 p atients with advanced seminoma were randomly assigned to treatment with eit her single agent carboplatin (C) at a dose of 400 mg/m(2) to be corrected f or glomerular filtration rate outside the range 81-120 ml min(-1) and to be administered on day 1 of a 21 day cycle to a total of 4 cycles or to etopo side + platinum (EP). The trial was designed as an equivalence study aiming to exclude a reduction in the 3-year progression-free survival in patients allocated to carboplatin of between 10 and 15%, requiring initially a targ et accrual of 250 patients (90% power significance level 5% (one-sided)). T he trial closed after 130 patients had been randomized following recommenda tion by an independent data monitoring committee. At a median follow-up tim e of 4.5 years, 81% of patients had been followed up for at least 3 years a nd 19 patients have died. The estimated PFS rate (95% Confidence Intervals (CI)) at 3 years was 71% (60-82%) in patients allocated C and 81% (71-90%) in those allocated EP; the 95% CI for the difference in 3 year PFS was -6% to +19%. The hazard ratio of 0.64 (95% CI 0.32-1.28) favoured EP but the di fference was not statistically significant (log rank chi-squared = 1.59 P = 0.21). The 3-year survival rate was 84% (75-92%) in those allocated C, and 89% (81-96%) in those allocated EP. The hazard ratio for survival was 0.85 with 95% CI, 0.35-2.10, log rank chi-squared = 0.12, P = 0.73. The trial h as not demonstrated statistically significant differences in the major surv ival endpoints comparing single agent carboplatin with a combination of eto poside + cisplatin. This cannot be taken as an indication of equivalence si nce the limited size of this trial rendered it unable to exclude a 19% lowe r progression-free survival and survival in those treated with single agent carboplatin which would be important clinically. Standard initial chemothe rapy for advanced seminoma should be based on cisplatin combinations and th e role of carboplatin awaits the outcome of further studies. (C) 2000 Cance r Research Campaign.