Dose-Escalation and Pharmacokinetic Study Following a Single Dose of Oxaliplatin in Cancer-Bearing Dogs

摘要

Oxaliplatin is more potent than cisplatin, lacks cross-resistance to other platinum agents, and has a favorable toxicity profile. This study's objective was to define the maximally tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin in cancer-bearing dogs. This was a prospective, single-patient-cohort, dose-escalation study of oxaliplatin in client-owned dogs with confirmed, spontaneous malignancy. A single infusion was administered; the starting dose was 50 mg/m(2), with 10 mg/m(2) escalation-increments if no DLT was documented, up to a maximum dose of 140 mg/m(2). Plasma total platinum was measured at multiple timepoints and patients were monitored weekly. Ten dogs were enrolled in single-patient-cohort treatment levels up to the maximum level of 140 mg/m(2). There were no DLTs, and the maximally tolerated dose was not determined. The area under the curve(0-7 days) for 100-140 mg/m(2) ranged from 77,850 to 82,860 ng/mL x hr; the area under the curve(0-4 hr) for 50-140 mg/m(2) was linear with dose (r(2) = 0.639, P = .0055). The data suggest a single infusion of oxaliplatin is well tolerated in cancer-bearing dogs up to 140 mg/m(2). There was good correlation between exposure and dose, while achieving plasma levels similar to therapeutic levels documented in humans.