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Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

Jalid Sehouli, Dirk Stengel, Guelten Oskay-Oezcelik, Alain G. Zeimet, Harald Sommer, Peter Klare, Martina Stauch, Axel Paulenz, Oumar Camara, Elke Keil, Werner Lichtenegger

From the Department of Gynecology, Charité University Medical Center; The Center for Clinical Research, Unfallkrankenhaus; Helios-Klinikum Berlin, Germany; Praxis for Gynecologic Oncology, Berlin; Ernst-Moritz-Arndt University of Greifswald, Greifswald; University of Jena, Jena; Ludwig-Maximilian-Universität of Munich, Munich; Klinikum Ernst-von-Bergmann Potsdam, Potsdam; Practice for Oncology and Hematology, Kronach, Germany; and the University of Innsbruck, Innsbruck, Austria

Corresponding author: Jalid Sehouli, MD, Humboldt-University, Department of Gynecology and Obstetrics, Carite/Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin 13353, Germany; e-mail: sehouli{at}aol.com

Purpose: The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.

Patients and Methods: Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m²/d, topotecan 1.0 mg/m² plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m²/d plus gemcitabine 800 mg/m² on day 1 and 600 mg/m² on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).

Results: The trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.

Conclusion: Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Supported by the German Cancer Society (DKG) and the North-Eastern German Society of Gynecological Oncology (NOGGO).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on www.JCO.org.