Clinical Evidence for Topotecan-Paclitaxel Non–Cross-Resistance in Ovarian Cancer

Purpose: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, 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/m2/d) 3 5 every 21 days (n 5 112) or paclitaxel (175 mg/m2 over 3 hours) every 21 days (n 5 114). 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 61 topotecan) and 10.2% (5 of 49 paclitaxel; P 5 .638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (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 topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). Conclusion: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non–cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.