DX-8951 displayed linear pharmacokinetic characteristics at the doses administered. Other side effects were not more than grade 2, and included gastrointestinal dysfunction, stomatitis, dermatitis, alopecia, liver dysfunction and drug fever. Grade 3 nonhematologic side effects included nausea (25% of patients) and fatigue (19%). Grade 3 or more anemia and thrombocytopenia were seen in 25% and 13% of patients, respectively. One episode of neutropenic fever was observed. The main toxic effect was neutropenia and leukopenia with 50% of patients experiencing grade 3 or 4 neutropenia and leukopenia. The median overall survival was 117 days (95% CI 90–279 days). The median time to tumor progression was 43 days (95% CI 37–92 days). Results Disease was stable in 7 of 16 patients (44%) (4 minor response and 3 stable disease). The pharmacokinetic and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. Treatment consisted of a daily infusion of DX-8951f at 0.3 mg/m2 per day (except for one minimally pretreated patient who started at 0.5 mg/m2 per day) over 30 min for five consecutive days every 3 weeks. All 16 patients were assessable for safety and 15 for efficacy analyses. Anderson Cancer Center were 16 patients with measurable cancer resistant to platinum, taxane and topotecan.
Methods Enrolled in the study at The University of Texas M. The objectives of this phase II study were to determine the antitumor activity, safety and pharmacokinetic profile of DX-8951f administered intravenously for five consecutive days, every 3 weeks in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. Background DX-8951f is a water-soluble camptothecin derivative with greater in vivo and in vitro activity than topotecan or irinotecan.
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