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Publication : Fenretinide therapy in prostate cancer: effects on tissue and serum retinoid concentration.

First Author  Thaller C Year  2000
Journal  J Clin Oncol Volume  18
Issue  22 Pages  3804-8
PubMed ID  11078493 Mgi Jnum  J:66202
Mgi Id  MGI:1928123 Doi  10.1200/JCO.2000.18.22.3804
Citation  Thaller C, et al. (2000) Fenretinide therapy in prostate cancer: effects on tissue and serum retinoid concentration. J Clin Oncol 18(22):3804-8
abstractText  PURPOSE: To examine the feasibility of using fenretinide (4-HPR) for the prevention 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 placebo for 4 weeks before undergoing a radical prostatectomy. RESULTS: Prostate tumors in mice treated with 4-HPR contained high levels of 4-HPR and of all-trans-retinoic acid (RA) and reduced levels of retinol (ROH). Patients given 4-HPR were found to have significantly higher concentrations 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 found in mice and were far below the concentrations reported in human breast tissue. Serum and tissue ROH levels were reduced to less than half the concentrations found in untreated controls. RA 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.
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