Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors

Background: Oxaliplatin, a platinum compound, has been commonly used around the world for treating advanced colorectal cancer. The generally recommended dose and schedule of oxaliplatin monotherapy is 130 mg/m² every 3 weeks. This trial was conducted to evaluate the safety and pharmacokinetics of oxaliplatin monotherapy in Japanese patients with solid tumors. Methods: Oxaliplatin was administered as a 2-h intravenous infusion every 3 weeks at a dose of 90 and 130 mg/m². Blood was collected to determine the total platinum and the ultrafiltrate platinum concentrations in plasma in all cycles. Results: Nine patients were enrolled; three were given oxaliplatin monotherapy at 90 mg/m² and six received 130 mg/m². All tumors were colorectal cancer. The major adverse reactions included myelosuppressive, neurological and gastrointestinal toxicities, although most were grades 1 and 2 at both dose levels. Peripheral sensory neuropathy of without movement disturbance (grade 1 or 2) was observed in all patients at both dose levels. The 130 mg/m² dose level was not found to be the maximum tolerated dose, but was judged to be the recommended dose. No objective responses were seen and five cases of no change were observed. A bi-exponential open model best described the disappearance of platinum in the plasma, and a tri-exponential open model best described the disappearance of ultrafilterable platinum in the plasma at both dose levels. No racial difference was suggested in the pharmacokinetics of oxaliplatin. Conclusions: The oxaliplatin monotherapy dose schedule of 130 mg/m² every 3 weeks, recommended worldwide, is acceptable for Japanese patients.