A phase I trial of a 3-day topotecan Q 21 days for recurrent epithelial cancers of the ovary, fallopian tube, and peritoneum

Objective. This trial was undertaken to determine the dose limiting toxicit y (DLT) and maximum tolerated dose (MTD) of topotecan that can be administe red for 3 days q 21 days. A 3-day schedule is more convenient and less expe nsive than standard 5-day dosing, Methods. Patients with recurrent epithelial ovary, tubal, or peritoneal car cinoma were treated with escalating doses of topotecan beginning at 2.50 mg /m(2) as an outpatient days 1-3 q 21 days. Colony stimulating factors were not employed prophylactically, but could be added for grade 4 marrow toxici ty. Results. Twenty patients with a median age of 61 (range 46-80) and performa nce status of 0 or 1 were entered. All patients had received at least one p rior paclitaxel/platinum regimen; 6 had received two. Ninety-one cycles wer e delivered (median = 6) and 98.9% were on schedule. Grade 4 neutropenia wa s 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 associate d with febrile neutropenia, Two patients experienced grade 4 neurotoxicity (DLT) at 4.25 mg/m(2), Other nonhematologic toxicity was mild, Conclusions. Topotecan can be safely administered on schedule as an outpati ent days 1-3 q 21 days, Neurotoxicity was the DLT when G-CSF was added; the MTD was 3.75 mg/m(2). There was minimal other nonhematologic toxicity, Neu tropenia was predictable and easily managed with G-CSF, Febrile neutropenia was uncommon and thrombocytopenia was rare at the doses evaluated. (C) 200 0 Academic Press.