Abstract
The aim of this study was to determine the dose of weekly oral topotecan that allows safe administration and to evaluate the pharmacokinetics of this dose in patients with recurrent gynecologic malignancies. The first cohort of patients received oral topotecan 6 mg/week administered orally on days 1, 8, and 15 of a 28-day regimen. A standard 3+3 dose-escalating phase design was used for dose levels II-V (8, 10, 12 and 14 mg/week). Toxicity was scored according to the Common Terminology Criteria for Adverse Events. Cumulative toxicity was summarized in the 6-12 mg/week combined cohort and 14 mg/week cohort separately. Pharmacokinetic samples were obtained for day 1, cycle 1 only in the expansion cohort (dose level V). Twenty-five patients received a total of 88 cycles of therapy. Hematologic toxicities of grade 3 (6-12 mg dose) were neutropenia (25%) and anemia (8.3%). Gastrointestinal toxicities of grade 3 were diarrhea (16.7%) and obstruction (8.3%, disease-related). Grade 3 or 4 (14 mg/week) hematologic toxicities consisted of neutropenia (38.5%), platelets (15.4%), anemia (15.4%), infection with neutropenia (7.7%), and thrombosis (7.7%). Gastrointestinal toxicities of grade 3 were diarrhea (7.7%), obstruction (7.7%), and vom...Continue Reading
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