DX-8951f, a Hexacyclic Camptothecin Analog, on a Daily-Times-Five Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies

PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dos...