Phase II evaluation of three-day topotecan in recurrent platinum-sensitive ovarian carcinoma: A gynecologic oncology group study

BACKGROUND. Topotecan, administered intravenously at a dose of 1.5 mg/m² per day for 5 days every 21 days, is an established regimen in the treatment of recurrent ovarian carcinoma. Alternate dosing strategies have sought to improve toxicity. The authors evaluated the tolerability and antitumor activity of a 3-day topotecan regimen. METHODS. A multicenter Phase II study, which included patients with platinum-sensitive ovarian carcinoma, was conducted. Patients were to receive an intravenous dose of topotecan of 2.0 mg/m² per day for 3 days every 21 days until disease progression or unacceptable toxicity occurred. Doses were modified in 0.25-mg/m² increments based on tolerability. Granulocyte-colony-stimulating factor support was used as necessary. RESULTS. From February to June 2000, 30 patients were enrolled. Their median age was 56 years (range, 41-81 years). Twenty-nine patients were evaluable for toxicity and efficacy. A median of 5 courses (range, 1-11 courses) of topotecan was administered. Eighteen of 30 (60%) patients experienced Grade 4 neutropenia. There was one report each of Grade 4 thrombocytopenia, anemia, and gastrointestinal toxicity (grading performed according to National Cancer Institute Common Toxicity Criteria). Ten patients developed Grade 3 leukopenia and 9 had Grade 3 neutropenia. Serious nonhematologic events were rare. There were 2 (7%) complete and 2 (7%) partial responses, for an overall response rate of 14%. Sixteen (55%) patients had stable disease and 9 (31%) experienced disease progression. CONCLUSIONS. A 3-day regimen of topotecan at a dose of 2.0 mg/m² per day was generally well tolerated, although the response rate was lower than that for the standard 5-day schedule.