Clinical evidence for topotecan-paclitaxel non-cross-resistance in ovarian cancer

M. Gore, W. Ten Bokkel Huinink, J. Carmichael, A. Gordon, N. Davidson, R. Coleman, M. Spaczynski, J. F. Héron, G. Bolis, H. Malmström, J. Malfetano, C. Scarabelli, P. Vennin, G. Ross, S. Z. Fields

Research output: Contribution to journalArticlepeer-review


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) × 5 every 21 days (n = 112) or paclitaxel (175 mg/m2 over 3 hours) every 21 days (n = 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 = .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-cress-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Original languageEnglish
Pages (from-to)1893-1900
Number of pages8
JournalJournal of Clinical Oncology
Issue number7
Publication statusPublished - Apr 1 2001

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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