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/m2) was administered daily (days 1-5) followed by etoposide (50mg/m2) 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 < 1000/μl or platelets < 50,000/μl before completing administration of etoposide or topotecan; neutropenic fever; platelets < 20,000/μl; or a delay greater than 2 weeks in starting cycle 2 due to hematologic toxicity (ANC < 1500/μl or platelets < 100,000/μl on scheduled day of treatment). 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,itmay be necessary to hold therapy the thirdweek. Based on the activity seen in this patient population,it is planned to take this regimen into a phase II setting. 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 of Topotecan (0.8 mg / m2) were administered daily (days 1-5) followed by etoposide (50 mg / m2) 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 <1000 / μl or platelets <50,000 / μl before completing courses Administration of etoposide or topotecan; neutropenic fever; platelets <20,000 / μl; or a delay greater than 2 weeks in starting cycle 2 due to hematologic toxicity (ANC <1500 / μl or platelets <100,000 / μl on scheduled day of treatment) ts.: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. 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, itmay be necessary to hold therapy the thirdweek. Based on the activity seen in this patient population, it is planned to take this regimen into a phase II setting.