Effect of the synthetic retinoid fenretinide on circulating free prostate-specific antigen, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 levels in men with superficial bladder cancer.
OBJECTIVE
Fenretinide (4-HPR) is a synthetic retinoid that has shown a preventive activity in prostate cancer animal models.


METHODS
We measured the changes in total and free prostate-specific antigen (PSA) and its association with insulin-like growth factor I (IGF-I) and IGFBP-3 levels after 1 year of treatment in 24 subjects given 4-HPR and 24 control subjects enrolled in a randomized bladder cancer prevention trial.


RESULTS
No significant effect of 4-HPR was observed on total and free fraction of PSA levels. The median percentage [95 confidence interval (95% CI)] change for % free PSA and total PSA in the 4-HPR and the control group were, respectively, 7.6 (95% CI, -4.0 to 69.3) versus 5.1 (95% CI, -21.4 to 59.8) and -7.8 (95% CI, -18.2 to 52.5) versus -12.3 (95% CI, -44.6 to 9.6). However, in patients ages <60 years, there was a trend to an increase of total free PSA and % free PSA after treatment with 4-HPR that was different from a trend to a decrease in the control group (P = 0.002 and 0.052, respectively). The interaction between age and treatment was statistically significant on free PSA (P = 0.001). A similar pattern was noted with smoking status (P = 0.011 for the interaction on free PSA). No association was observed between PSA levels and IGF-I or IGFBP-3 levels.


CONCLUSIONS
We conclude that 4-HPR has no significant effect on circulating PSA, but it increases significantly free PSA levels in subjects younger than 60 years and in nonsmokers. These effects might support an activity in prostate cancer prevention but further studies are required.
Serrano
Davide
D
Division of Chemoprevention, Cancer Epidemiology Center, Cancer Council of Victoria, Melbourne, Australia.
Baglietto
Laura
L
Johansson
Harriet
H
Mariette
Frederique
F
Torrisi
Rosalba
R
Onetto
Marina
M
Paganuzzi
Michela
M
Decensi
Andrea
A
D000367:Age Factors; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D012907:Smoking / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control
D016588:Anticarcinogenic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D017313:Fenretinide; D007334:Insulin-Like Growth Factor I; D017430:Prostate-Specific Antigen