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
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.