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 × 10-6 m. There was little drug accumulation on this schedule, as trough concentrations between p.o. doses often dropped below 1 × 10-6 m. 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.
↵2 Recipient of a Gordon E. Richards Fellowship from the Canadian Cancer Society. To whom requests for reprints should be addressed, at Building 10, Room 6N119, National Cancer Institute, Bethesda, Md. 20205.
- Received June 22, 1981.
- Accepted January 19, 1982.
- ©1982 American Association for Cancer Research.