A Phase I Trial of a 3-Day Topotecan Q 21 Days for Recurrent Epithelial Cancers of the Ovary, Fallopian Tube, and Peritoneum

Abstract

Objective. This trial was undertaken to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of topotecan that can be administered for 3 days q 21 days. A 3-day schedule is more convenient and less expensive than standard 5-day dosing.Methods. Patients with recurrent epithelial ovary, tubal, or peritoneal carcinoma were treated with escalating doses of topotecan beginning at 2.50 mg/m2 as an outpatient days 1–3 q 21 days. Colony stimulating factors were not employed prophylactically, but could be added for grade 4 marrow toxicity.Results. Twenty patients with a median age of 61 (range 46–80) and performance status of 0 or 1 were entered. All patients had received at least one prior paclitaxel/platinum regimen; 6 had received two. Ninety-one cycles were delivered (median = 6) and 98.9% were on schedule. Grade 4 neutropenia was seen in 17 of 20 patients (85%) in cycle 1 and in 38 of 91 (41.8%) total cycles. Sixteen of 20 patients (80%) started G-CSF on cycle 2. Two of 91 (2.2%) cycles had grade 4 thrombocytopenia. Four cycles (4.4%) were associated with febrile neutropenia. Two patients experienced grade 4 neurotoxicity (DLT) at 4.25 mg/m2. Other nonhematologic toxicity was mild.Conclusions. Topotecan can be safely administered on schedule as an outpatient days 1–3 q 21 days. Neurotoxicity was the DLT when G-CSF was added; the MTD was 3.75 mg/m2. There was minimal other nonhematologic toxicity. Neutropenia was predictable and easily managed with G-CSF. Febrile neutropenia was uncommon and thrombocytopenia was rare at the doses evaluated.