A phase I trial of gemcitabine and topotecan in previously treated ovarian or peritoneal cancer: A Gynecologic Oncology Group study

Abstract Objective. To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer. Methods. Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gemcitabine at a dose of 800 mg/m 2 on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m 2 on days 2–5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort I, Dose Levels 1–5) then for gemcitabine (Cohort II, Dose Levels 6–9) until the MTD was reached. Results. Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2–4 (Dose Level −1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level −1, and the study was closed early. Conclusions. At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced dose-limiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.