PHASE I STUDIES OF ORAL SYNTHETIC RETINOIDS - 4-HPR

需要进行第一阶段的研究，以提供参数和特性

Phase I studies are needed to provide the parameters and characteristics of acute human toxicity, establish a maximally tolerated dose, delineate basic pharmacokinetics, and indicate a starting clinical dose for Phase III trials of the investigational drug. Based on the in vitro and in vivo evidence that vitamin A and its synthetic analogs are active in the neoplasia process and case reports demonstrating the successful chemoprevention of basal cell carcinoma with large doses of the retinoid isotretinoin, a Phase I intramural clinical trial of a promising new oral synthetic retinoid, 4-HPR (N-4-[hydroxyphenyl]-retinamide), has been implemented. This study has the following objectives: Delineate acute human toxicity patters of orally administered 4-HPR Determine a maximum tolerated/feasible dose (MT/FD) Evaluate the subacute toxicity of the MT/FD for 3 months Observe evidence of any therapeutic effect on specific cutaneous diseases and disorders of keratinization. Five patients in good general health but with multiple basal cell carcinomas initiated therapy at 800 mg/day. Toxicity was observed within 3 weeks in 3 different patients and further testing was discontinued.