Phase I Study of Oxaliplatin in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction (Summary Last Modified 04/2000)

OBJECTIVES: I. Determine the maximum tolerated dose of oxaliplatin in patients with advanced malignancies and varying degrees of liver dysfunction. II. Determine the effects of hepatic dysfunction on the plasma pharmacokinetics and pharmacodynamics of oxaliplatin in these patients. OUTLINE: This is a dose escalation, multicenter study. Patients are stratified according to liver function as defined by the following: Group A: Normal liver function - Bilirubin, SGOT, and alkaline phosphatase no greater than upper limit of normal (ULN) Group B: Mild liver dysfunction - Bilirubin no greater than ULN; SGOT greater than ULN to 2.5 times ULN and/or alkaline phosphatase greater than ULN to 5 times ULN Group C: Moderate liver function - Bilirubin greater than ULN to 3.0 mg/dL and/or SGOT greater than 2.5 times ULN and/or alkaline phosphatase greater than 5 times normal Group D: Severe liver dysfunction - Bilirubin greater than 3.1 mg/dL and any SGOT or alkaline phosphatase Group E: Patients who have received a liver transplant Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients in groups B, C, and D receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose- limiting toxicity. PROJECTED ACCRUAL: Approximately 72 patients will be accrued for this study within 1.5 years.