To determine the tolerability of oral maintenance topotecan when administered to patients with advanced ovarian, fallopian tube, and primary peritoneal serous cancers who have achieved a complete clinical response after first-line platinum-based therapy. Oral topotecan was given at a starting dose of 0.4 mg/m(2)/dose, twice a day (BID) for 21 consecutive days out of 28 days. The dose was subsequently increased to 0.5 mg/m(2)/dose, twice a day as tolerated. If the patient experienced toxicities during cycle 1 or subsequent cycles, doses were delayed and/or reduced. The lowest dose allowed on protocol was 0.3 mg/m(2)/dose twice daily. Thirteen patients were enrolled in the study, representing a total of fifty-nine cycles of oral topotecan. The starting dose of 0.4 mg/m(2) by mouth (PO) BID for 21 days was generally difficult for patients to tolerate, usually due to progressive anemia and fatigue, and a dose reduction to 0.3 mg/m(2) was necessary in 10/13 patients. A median of six cycles was administered, although 6 of 13 patients could not tolerate the planned 6 cycles due to toxicity. Hematologic toxicity was the most common side effect, although there were no episodes of febrile neutropenia. Diarrhea was the most common nonhematologic side effect, occurring in 8 of 13 patients. Six patients were removed from the study prior to completing the planned six cycles of therapy, after receiving a median number of 2.5 cycles of treatment. This dose and schedule of oral topotecan does not appear to be feasible in this patient population.