Topotecan, a semi-synthetic derivative of camptothecin, is an antitumor drug with topoisomerase I-inhibitory preclinical activity against various tumor types. The antitumor effect of topotecan in preclinical models was shown to be administration schedule-dependent as repeated bolus injections proved more effective than a single infusion. A number of different dosing schedules are being investigated in clinical trials including oral administration, a daily infusion on 5 consecutive days and a continuous infusion for 21 days. Previous studies of topotecan showed activity against platinum-resistant ovarian cancer using this variety 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 neutropenia, as dose-limiting toxicity. Phase II studies confirmed the antitumor activity of topotecan in platinum-failed diseases with an overall response rate ranging from 14% to 25%. A randomized Phase III study comparing topotecan with paclitaxel showed topotecan to have a higher response rate, 20.5% versus 13.2% (P=.138). Median times to progression 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 the topotecan arm than in the paclitaxel arm (79% vs 23%). Conclusion: topotecan in a daily administration for five days is an effective regimen as second- line treatment in ovarian carcinoma. Its efficacy manifested by higher response rates and significantly longer time to progression is comparable to paclitaxel. Further investigations on topotecan in ovarian cancer, including first-line use and combination with other active agents, are needed.
|Issue number||6 SUPPL. 2|
|Publication status||Published - Nov 1997|
ASJC Scopus subject areas
- Cancer Research