Published in Cancer Detection and Prevention 2000; 24(4):369-375.

Ocular Effects of Fenretinide, a Vitamin A Analog, in a Chemoprevention Trial of Bladder Cancer

Laura Baglietto, MSC,a Rosalba Torrisi, MD,c Giuseppe Arena, BSc,d Francesca Tosetti, PhD,d Allana Guerrieri Gonzaga, MSC,b Wanda Pasquetti, MD,e Chris Robertson, PhD,a and Andrea Decensi, MDb

aDivision of Epidemiology and Biostatistics and bChemoprevention Unit, European Institute of Oncology, Milan, and Departments of cMedical Oncology II, dMolecular Biology, and eClinical Pathology, National Institute for Cancer Research, Genoa, Italy

Address all correspondence and reprint requests to: Andrea Decensi, MD, Chemoprevention Unit, European Institute of Oncology, via Ripamonti, 435, 20141 Milan, Italy.

ABSTRACT: 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.

KEY WORDS: fenretinide, chemoprevention, night vision, vitamin A.