Clinical evidence for topotecan-paclitaxel non-cross-resistance in ovariancancer

Purpose: A large, randomized study comparing the efficacy and safety of top otecan versus paclitaxel in patients with relapsed epithelial ovarian cance r showed that these two compounds have similar activity. In this study, a n umber of patients crossed over to the alternative drug as third-line therap y, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. Patients and Methods: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 da ys (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 11 4). A total of 110 patients received crossover therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. Results: Response rates to third-line cross-over therapy were 13.1% (8 of 6 1 topotecan) and 10.2% (5 of 49 paclitaxel; P = .638). Seven patients who r esponded to third-line topotecan and four patients who responded to paclita xel had failed to respond to their second-line treatment. Median time to pr ogression (from the start of third-line therapy) was 9 weeks in both groups , and median survival was 40 and 48 weeks for patients who were receiving t opotecan or paclitaxel, respectively, The principal toxicity was myelosuppr ession; grade 4 neutropenia was more frequent with topotecan (81.4% of pati ents) than with paclitaxel (22.9% of patients). Conclusion: Topotecan and paclitaxel have similar activity as second-line t herapies with regard to response rates and progression-free and overall sur vival. We demonstrated that the two drugs have a degree of non-cross-resist ance. Thus, there is a good rationale for incorporating these drugs into fu ture first-line regimens, (C) 2001 by American Society of Clinical Oncology .