Sequential prolonged oral topotecan and prolonged oral etoposide as second-line therapy in ovarian or peritoneal carcinoma: A phase I Gynecologic Oncology Group study

Abstract Objective. Preclinical models suggest synergy when topoisomerase I and II inhibitors are given sequentially, but not simultaneously. A phase I study was conducted in previously treated ovarian or peritoneal carcinoma to determine the tolerability (maximum number of days) of sequential oral topotecan and oral etoposide. Methods. Topotecan (0.8 mg/m 2 ) was administered daily (days 1–5) followed by etoposide (50 mg/m 2 ) administered daily for up to 5 days (days 8–12). Patients on dose levels 3 and 4 repeated topotecan for up to 5 days starting on day 15 after the initial topotecan and etoposide sequence. Cycles were repeated every 28 days. Dose-limiting toxicities (DLT) were defined as: neutrophils Results. Nineteen patients were entered into this trial, and a total of 54 cycles (range 1–10) of therapy were administered. Dose-limiting toxicities, principally neutropenia, occurred when therapy was administered for 3 of 4 weeks. Conclusion. Oral topotecan and oral etoposide administered at these doses daily for 5 days sequentially for a maximum of three (out of every four) weeks of therapy are tolerable. In some cases, it may be necessary to hold therapy the third week. Based on the activity seen in this patient population, it is planned to take this regimen into a phase II setting.