Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer

Citation
L. Baglietto et al., Ocular effects of fenretinide, a vitamin A analog, in a chemoprevention trial of bladder cancer, CANCER DET, 24(4), 2000, pp. 369-375
Citations number
32
Categorie Soggetti
Oncology
Journal title
CANCER DETECTION AND PREVENTION
ISSN journal
0361090X → ACNP
Volume
24
Issue
4
Year of publication
2000
Pages
369 - 375
Database
ISI
SICI code
0361-090X(2000)24:4<369:OEOFAV>2.0.ZU;2-H
Abstract
Fenretinide is a vitamin A derivative under investigation in cancer prevent ion trials. Because all available pharmacologic and toxicologic data were o btained from breast cancer patients, we measured plasma drug, metabolite, a nd vitamin A levels and studied their relationship with visual and ocular s ymptoms in a cohere formed mostly by male subjects belonging to a bladder c ancer prevention trial. After 1 year, the mean plasma retinol levels (1 sta ndard deviation [SDI) 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). Pl asma retinol levels were correlated inversely to drug and metabolite concen trations, 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 int erval, 2.9-66.1). Although compliance as assessed by capsule count was high , three subjects originally assigned to the treatment group who proved to b e noncompliers (8.8%, or 3 of 34) had no detectable plasma drug or metaboli te levels. Our data confirm the specific pharmacologic and visual effects o f fenretinide also in a male population and strengthen the importance of mu ltiple blood measurements to monitor treatment compliance in prevention tri als.