TOPOTECAN, A NEW DRUG FOR THE TREATMENT O F EPITHELIAL OVARIAN-CANCER

Topotecan, a semi-synthetic derivative of camptothecin, is an antitumo r drug with topoisomerase I-inhibitory preclinical activity against va rious tumor types. The antitumor effect of topotecan in preclinical mo dels was shown to be administration schedule-dependent as repeated bol us injections proved more effective than a single infusion. A number o f different dosing schedules are being investigated in clinical trials including oral administration, a daily Infusion on 5 consecutive days and a continuos infusion for 21 days. Previous studies of topotecan s howed activity against platinum-resistant ovarian cancer using this va riety of schedules. The five-daily schedule repeated every 21 days was identified for further Phase II trials because It seemed to show the greatest activity in Phase I trials, with myelosuppression, mostly neu tropenia, as dose-limiting toxicity. Phase II studies confirmed the an titumor activity of topotecan in platinum-failed diseases with an over all response rate ranging from 14% to 25%. A randomized Phase III stud y comparing topotecan with paclitaxel showed topotecan to have a highe r response rate, 20.5 % versus 13.2 % (P=.138). Median times to progre ssion were 23 and 14 weeks, respectively, for topotecan and paclitaxel (P=.002), Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P=.515). Neutropenia was significantly more frequent in t he topotecan arm than in the paclitaxel arm (79% vs 23%). Conclusion: topotecan in a daily administration for five days is an effective regi men as second-line treatment in ovarian carcinoma. Its efficacy manife sted by higher response rates and significantly longer time to progres sion is comparable to paclitaxel. Further Investigations on topotecan in ovarian cancer, including first-line use and combination with other active agents, are needed.