Safety of the synthetic retinoid fenretinide: Long-term results from a controlled clinical trial for the prevention of contralateral breast cancer

Purpose: To describe the pattern of occurrence of adverse events commonly a rising during treatment with fenretinide, a synthetic retinoid under invest igation for cancer prevention. Patients and Methods: The series includes 2,867 women accrued in a trial ai med at assessing the effect of fenretinide on the prevention of second brea st ma lignancy. Women were randomly assigned to receive no treatment (1,435 patients) or 5-year fenretinide treatment (1,432 patients). In terms of di sease recurrence in the breast, the trial showed a possible beneficial effe ct of the compound in premenopausal women, and an opposite trend in postmen opausal women. End points considered for safety assessment were the occurre nce of diminished dark adaptation, dermatologic disorders, gastrointestinal symptoms, disorders of the ocular surface, and abnormal laboratory valves. Results: The most common adverse events were diminished dark adaptation (cu mulative incidence, 19.0%) and dermatologic disorders(18.6%). Less common e vents were gastrointestinal symptoms (13.0%) and disorders of the ocular su rface(10.9%). In comparison, incidence figures in the control arm were 2.9% for diminished dark adaptation, 2.9% for dermatologic disorders, 5.4% for gastrointestinal symptoms, and 3.2% for disorders of the ocular surface. Sy mptoms occurring during fenretinide treatment tended to recover with time. No between-group difference was observed for the occurrence of laboratory d ata abnormalities. Overall, 63 (4.4%) treatment discontinuations were cause d by adverse events. Conclusion: Given the number of patients involved in the study and the prol onged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retin oid. (C) 2001 by American Society of Clinical Oncology.