Abstract | PURPOSE: MATERIALS AND METHODS: 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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Authors | C Thaller, M Shalev, A Frolov, G Eichele, T C Thompson, R H Williams, O Dillioglugil, D Kadmon |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 18
Issue 22
Pg. 3804-8
(Nov 15 2000)
ISSN: 0732-183X [Print] United States |
PMID | 11078493
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Placebos
- Vitamin A
- Fenretinide
- Tretinoin
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Topics |
- Aged
- Animals
- Antineoplastic Agents
(blood, pharmacokinetics, therapeutic use)
- Double-Blind Method
- Fenretinide
(blood, pharmacokinetics, therapeutic use)
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Placebos
- Prostatectomy
- Prostatic Neoplasms
(drug therapy, metabolism, surgery)
- Tretinoin
(blood, metabolism)
- Vitamin A
(blood, metabolism)
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