Fenretinide therapy in prostate cancer: Effects on tissue and serum retinoid concentration

Purpose: To examine the feasibility of using fenretinide (4-HPR) for the pr evention and treatment of prostate cancer. Materials and Methods: We measured the impact of 4-HPR therapy on retinoid concentrations in vivo, in a mouse model of prostate cancer and clinically, in patients with prostate cancer who were given oral 4-HPR (200 mg/d) or p lacebo for 4 weeks before undergoing a radical prostatectomy. Results: Prostate tumors in mice treated with 4-HPR contained high levels o f 4-HPR and of all-trams-retinoic acid (RA) and reduced levels of retinol ( ROH). Patients given 4-HPR were found to have significantly higher concentr ations of 4-HPR in the cancerous prostate as compared with the serum levels (463 nmol/L v 326 nmol/L; P =,049), but they were only 1/10 the levels fou nd in mice and were far below the concentrations reported in human breast t issue. Serum and tissue ROH levels were reduced to less than half the conce ntrations found in untreated controls. PA concentrations in human serum and in cancerous prostates were not significantly affected by 4-HPR treatment, in contrast with the findings in mice. Conclusion: The standard oral dose of 4-HPR proposed for breast cancer (200 mg/d) achieved only modest drug levels in the prostate and is unlikely to be effective for prostate cancer prevention or treatment. Higher doses need to be explored. (C) 2000 by American Society of Clinical Oncology.