Mature results of a prospective randomized trial comparing a three-weekly with an accelerated weekly schedule of cisplatin in advanced ovarian carcinoma

In a retrospective analysis of a series of clinical trials by Levin and Hry niuk in 1987, the average relative dose intensity of first-line chemotherap y for advanced ovarian cancer correlated significantly with clinical respon se and survival, and cisplatin was the only drug for which the outcome corr elated with the individual drug relative dose intensity. There was a need t o test whether and to what extent this evidence would be confirmed in a pro spective evaluation. In this study 101 patients with advanced ovarian carci noma were randomized to receive the same total dose of cisplatin but at the conventional 3-weekly schedule (CTWS) (100 mg/m(2) every 3 weeks for six c ycles) (51 patients) or at an experimental accelerated weekly schedule (AWS ) (100 mg/m2 every week for two triplets of three cycles separated by a 5-w eek interval) (50 patients). To benefit from a multidrug regimen at the sam e extent, patients in both arms sequentially received four cycles of doxoru bicin and cyclophosphamide. The median follow-up period of this study is 9. 7 years. In 42 and 40 patients of the two arms having evaluable response, t he clinical complete response rates to cisplatin were 14% and 22% and the c omplete plus partial response rates were 48% and 55% in the CTWS and in the AWS arm, respectively. These differences were not statistically significan t. However, the survival curves were similar during the first 2 years but c learly diverged thereafter in favor of the AWS arm (p = 0.07). At 5 years, 12% and 30% of the patients were still alive in the CTWS and in the AWS arm , respectively. Hematologic toxicity was not relevant in either arm of the study. Nonhematologic toxicity, especially ototoxicity, was substantial and significantly higher in the AWS arm. Although statistically nonsignificant , this AWS regimen of cisplatin is associated with long-term better surviva l compared to the CTWS regimen in advanced ovarian carcinoma. This accelera ted approach administering cisplatin should be further investigated, especi ally in patients with low residual disease after primary surgery.