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Topotecan/cisplatin inferior to carboplatin/paclitaxel in epithelial ovarian cancer

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CHICAGO — The combination of topotecan plus cisplatin followed by paclitaxel plus carboplatin did not show improved efficacy for the treatment of epithelial ovarian cancer when compared with the standard therapy of carboplatin plus paclitaxel.

Paul J. Hoskins, MD, of the British Columbia Cancer Agency, presented the results of the Gynecologic Cancer Intergroup Study at the 2008 ASCO Annual Meeting.

“Topotecan [Hycamtin, GlaxoSmithKline] has single-agent activity in resistant, recurrent epithelial ovarian cancer,” Hoskins said during his presentation. “However, sequenced topotecan doublet followed by paclitaxel treatment did not show a benefit in progression-free survival or response rates.”

In the study, 819 patients were randomly assigned to receive either four cycles of topotecan plus paclitaxel followed by four cycles paclitaxel plus carboplatin (n=409) or eight cycles of paclitaxel plus carboplatin (n=410).

The median progression-free survival for patients in the experimental arm was 14.6 months compared with 16.2 months in the standard therapy arm (HR=1.1; 95% CI, 0.94-1.28). In addition, patients in the experimental arm had more grade 3/4 febrile neutropenia (9.9%) compared with the standard treatment arm (2.7%).

“There are now a multitude of studies using topotecan and none of them show advantages,” Hoskins said. “Paclitaxel plus carboplatin should remain the standard of care for advanced ovarian cancer.”

In the setting of advanced disease, international collaboration has improved the efficiency of clinical research, particularly in phase-3 trials. The intravenous carboplatin/paclitaxel regimen remains a well tolerated and effective standard but with limited impact on long-term mortality. Incorporation of topotecan has not been associated with improved outcomes either in frontline or maintenance settings.

– Michael A. Bookman, MD

Fox Chase Cancer Center

For more information:

• Hoskins PJ. A phase III trial of cisplatin plus topotecan followed by paclitaxel plus carboplatin versus standard carboplatin plus paclitaxel as first-line chemotherapy in women with newly diagnosed advanced epithelial ovarian cancer. A Gynecologic Cancer Intergroup Study of the NCIC CTG, EORTC, GCG, and GEICO. #LBA 5505. Presented at: the 2008 ASCO Annual Meeting; May 30-June 3; Chicago.