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

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, with 10 mg/m escalation-increments if no DLT was documented, up to a maximum dose of 140 mg/m. 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. There were no DLTs, and the maximally tolerated dose was not determined. The area under the curve for 100-140 mg/m ranged from 77,850 to 82,860 ng/mL × hr; the area under the curve for 50-140 mg/m was linear with dose (r = 0.639, . There was good correlation between exposure and dose, while achieving plasma levels similar to therapeutic levels documented in humans.