Vitamin A and its analogs (retinoids) have shown great promise for the chemoprevention of cancer as well as being a possible new class of chemotherapeutic agents. A Phase I and II trial of 13-cis-retinoic acid in advanced cancers was initiated, and the clinical pharmacology of the drug was studied. All patients received p.o. 13-cis-retinoic acid starting at 0.5 mg/kg/day, escalating over 4 weeks to a maximum dose of 8 mg/kg/day in divided doses. Although there was a linear correlation of plasma concentration with dose escalation, large interindividual variations in peak plasma concentrations were noted. At the maximum drug dose, the mean peak plasma concentration was 4 × 10-6m. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 × 10-6m. The drug was metabolized extensively to a metabolite, the concentrations of which exceeded parent 13-cis-retinoic acid concentrations with chronic dosing. Retinol concentrations were below the normal range.

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Presented in part at the American Society for Clinical Oncology Meeting, Washington, D. C., April 30, 1981.

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