Importance of topotecan in the therapy of ovarian carcinoma, today and tomorrow

Topotecan is a powerful inhibitor of DNA topoisomerase I, the cytostatic ac tivity of which has been demonstrated in preclinical and clinical studies. At the ASCO meeting in Los Angeles, 1998, the final results of a randomized phase III study were presented that compared topotecan and paclitaxel in t he second-line therapy of advanced ovarian carcinoma. This study is very va luable because its results were externally tested. In this study, a total o f 226 patients with platinum-containing pretreatment received therapy with topotecan (1.5 mg/m(2), 5 days, 30-min infusion: every 21 days) or with pac litaxel (175 mg/m(2); 3-hour infusion: every 21 days). The main toxicities of the therapy involved hematological side effects. Neutropenia, thrombocyt openia and anemia occurred more frequently on topotecan than on paclitaxel. However, the toxicities were not cumulative and were easily manageable. Th e non-hematological side effects were mild on the whole. The remission rate for topotecan was 20.6% [CR 5 patients (4.5%), PR 18 patients (16.1%)], wi th a median duration of remission of 28.7 weeks. For paclitaxel, a remissio n rate of 13.2% was obtained [CR 3 patients (2.6%), PR 12 patients (10.6%)] , with a progression-free interval of 27.6 weeks. There were no statistical ly significant differences between the two treatment arms. At the 1998 ASCO meeting, three phase I/II studies were presented that inte grated topotecan, as an effective agent in the therapy of advanced ovarian carcinoma, into a combination with cisplatin and paclitaxel for first line therapy. In these studies, both the dose of topotecan and the duration of i nfusion were varied. The combinations of cisplatin (50-75 mg/m(2)), paclita xel (110-175 mg/m(2); 24- or 3-hour infusion) and topotecan (0.3-0.6 mg/m(2 ), days 1-5), administered every 21 days, were feasible with the help of G- CSE The effectiveness of these combinations deserves investigation in phase II/III studies.