Journal Article

Randomized Phase III Trial of Topotecan Following Carboplatin and Paclitaxel in First-line Treatment of Advanced Ovarian Cancer: A Gynecologic Cancer Intergroup Trial of the AGO-OVAR and GINECO

Jacobus Pfisterer, Béatrice Weber, Alexander Reuss, Rainer Kimmig, Andreas du Bois, Uwe Wagner, Hugues Bourgeois, Werner Meier, Serban Costa, Jens-Uwe Blohmer, Alain Lortholary, Sigrid Olbricht, Anne Stähle, Christian Jackisch, Anne-Claire Hardy-Bessard, Volker Möbus, Jens Quaas, Barbara Richter, Willibald Schröder, Jean-François Geay, Hans-Joachim Lück, Walther Kuhn, Harald Meden, Ulrike Nitz and Eric Pujade-Lauraine

in JNCI: Journal of the National Cancer Institute

Volume 98, issue 15, pages 1036-1045
Published in print August 2006 | ISSN: 0027-8874
Published online August 2006 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/djj296
Randomized Phase III Trial of Topotecan Following Carboplatin and Paclitaxel in First-line Treatment of Advanced Ovarian Cancer: A Gynecologic Cancer Intergroup Trial of the AGO-OVAR and GINECO

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Background: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. Methods: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan–Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran–Mantel–Haenszel test. All statistical tests were two-sided. Results: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI = 0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86 to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3–4 hematologic toxic effects (requiring more supportive care) and more grade 3–4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm (P = .166). Conclusions: The sequential addition of topotecan to carboplatin–paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.

Journal Article.  6992 words.  Illustrated.

Subjects: Medical Oncology

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