Background: Phase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer.
Methods: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m2 day 1 and day 15) and topotecan (0.4 mg/m2 per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients.
Results: Thirty-eight patients received 144 cycles of therapy (median, 4; range, 1–6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%–46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%–71%). Three in each stratum had lengthy complete responses.
Conclusions: Biweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.
*Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT; †Division of Medical Oncology, Department of Medicine, and ‡Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY; §Beth Israel Cancer Center, Albert Einstein College of Medicine, NY; New York University School of Medicine, New York, NY, ∥Division of Biostatistics, Department of Population Health, New York University School of Medicine, New York, NY; ¶Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and #Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Achuta Kumar Guddati, MD, PhD, Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA. E-mail: firstname.lastname@example.org.
Presented in part at the American Society of Clinical Oncology meeting, June 2010.
Supported by the Department of Health and Human Services, National Cancer Institute contract number N01-CM-62204, New York Cancer Consortium (PI: Joseph A. Sparano, MD)
The authors declare no conflicts of interest.
Received May 20, 2013
Accepted August 4, 2013