Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer.
Fenretinide is a vitamin A derivative under investigation in cancer prevention trials. Because all available pharmacologic and toxicologic data were obtained from breast cancer patients, we measured plasma drug, metabolite, and vitamin A levels and studied their relationship with visual and ocular symptoms in a cohort formed mostly by male subjects belonging to a bladder cancer prevention trial. After 1 year, the mean plasma retinol levels (+/- standard deviation [SD]) were 168.2 +/- 75.8 ng/ml in 31 subjects treated with fenretinide and 594.5 +/- 168.4 ng/ml in 36 control subjects (P < .001). Plasma retinol levels were correlated inversely to drug and metabolite concentrations, which in turn were correlated inversely to the interval from last drug intake. The decline of plasma vitamin A levels accounted for a 41.7% cumulative incidence of diminished dark adaptability in the retinoid arm as compared to 6.8% in the control arm (odds ratio = 13.8; 95% confidence interval, 2.9-66.1). Although compliance as assessed by capsule count was high, three subjects originally assigned to the treatment group who proved to be noncompliers (8.8%, or 3 of 34) had no detectable plasma drug or metabolite levels. Our data confirm the specific pharmacologic and visual effects of fenretinide also in a male population and strengthen the importance of multiple blood measurements to monitor treatment compliance in prevention trials.
Baglietto
L
L
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
Torrisi
R
R
Arena
G
G
Tosetti
F
F
Gonzaga
A G
AG
Pasquetti
W
W
Robertson
C
C
Decensi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000009:adverse effects*; D002295:Carcinoma, Transitional Cell / Q000517:prevention & control*; D018890:Chemoprevention / Q000009:adverse effects; D003623:Dark Adaptation / Q000187:drug effects; D005260:Female; D017313:Fenretinide / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007765:Lacrimal Apparatus / Q000187:drug effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009755:Night Blindness / Q000139:chemically induced; D016017:Odds Ratio; D010349:Patient Compliance; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control*; D014785:Vision, Ocular / Q000187:drug effects*; D014801:Vitamin A / Q000097:blood
D016588:Anticarcinogenic Agents; D014801:Vitamin A; D017313:Fenretinide