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

Abstract

ABSTRACT 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 × 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.