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Published on: March 6, 2018
Fenretinide therapy in prostate cancer: effects on tissue and serum retinoid concentration
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.
Insights
Fenretinide (4-HPR) shows modest prostate drug levels at standard doses, suggesting it may not be effective for prostate cancer prevention or treatment. Higher doses require further investigation.
Area of Science:
- Oncology
- Pharmacology
- Retinoid Metabolism
Background:
- Fenretinide (4-HPR) is a synthetic retinoid with potential anticancer properties.
- Retinoids play a role in cell differentiation and apoptosis, relevant to cancer treatment.
- Understanding drug concentrations in target tissues is crucial for therapeutic efficacy.
Purpose of the Study:
- To assess the feasibility of fenretinide (4-HPR) in prostate cancer prevention and treatment.
- To measure retinoid concentrations in prostate tissue and serum following 4-HPR administration.
Main Methods:
- A mouse model of prostate cancer was used to evaluate 4-HPR impact on retinoid levels.
- Clinical study involved patients with prostate cancer receiving oral 4-HPR (200 mg/d) or placebo.
- Drug and retinoid levels were measured in serum and prostate tissue before radical prostatectomy.
Main Results:
- Mice treated with 4-HPR showed high levels of 4-HPR and all-trans-retinoic acid (RA), with reduced retinol (ROH).
- Patients achieved higher 4-HPR concentrations in cancerous prostate tissue than in serum, but levels were lower than in mice and human breast tissue.
- Serum and tissue ROH levels decreased, but RA concentrations were not significantly altered in human samples.
Conclusions:
- The standard oral dose of 4-HPR (200 mg/d) results in modest prostate drug levels, likely insufficient for effective prostate cancer prevention or treatment.
- Higher fenretinide doses should be explored to achieve potentially therapeutic concentrations in prostate cancer.
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