Chemoprevention of breast cancer with fenretinide (4-HPR): study of long-term visual and ophthalmologic tolerability.
Ключови думи
Резюме
BACKGROUND
Fenretinide (4-HPR) is a synthetic retinoid being clinically tested in the chemoprevention of different tumors and precancerous lesions. Though safer than many other retinoids in experimental models, in humans 4-HPR may induce adverse effects that mainly affect the eye and visual function. Such effects are thought to be caused by the reduction of plasma retinol levels, which occurs after administration of the retinoid.
METHODS
A series of 826 women treated with 4-HPR was studied to quantify the incidence and temporal pattern of occurrence of visual (dark adaptation) and ophthalmologic complaints (ocular dryness, lacrimation, conjunctivitis or photophobia) and to investigate the possible association between their occurrence and plasma retinol levels.
RESULTS
The cumulative incidence of visual complaints reached nearly 20% at 5 years. The occurrence of these symptoms was more frequent at the start of treatment. The probability of developing visual complaints was significantly higher in patients with lower plasma retinol concentrations following 4-HPR treatment. The cumulative incidence of ophthalmologic complaints was 8% at 5 years. The occurrence of these complaints was evenly distributed during treatment. Ophthalmologic complaints were not associated with a greater degree of reduction of plasma retinol concentrations, but rather with the patient's age, since symptomatic patients were generally older than asymptomatic patients.
CONCLUSIONS
Visual and ophthalmologic complaints are common during 4-HPR treatment; their estimated 5-year cumulative incidence is close to 20% and 8%, respectively. However, the pattern of occurrence over time and the underlying mechanisms of these two types of complaints seem different.
