Effect of fenretinide on ovarian carcinoma occurrence

Objective. The aim of this study was to update the effect of fenretinide, a synthetic vitamin A analogue proposed for chemo-prevention, on the occurrence of ovarian carcinoma. Methods. Data were obtained from a randomized clinical trial for the prevention of second breast cancer. For the present investigation, events of interest were new primary carcinomas of the ovary arising in the fenretinide or the no-treatment (control) arm. The probability of carrying a BRCA germ-line mutation was assessed in women with ovarian carcinoma according to G. Parmigiani et al. (1998, Am J Hum Genet 62, 145-58). Results. Fenretinide reduced ovarian carcinoma occurrence during the 5-year intervention period (0 versus 6 cases in the fenretinide and control arm, P = 0.0327). This effect was no longer evident after the 5-year intervention period (6 versus 4 cases, P = 0.7563). Therefore with median observation time of 121 months, a total of 6 carcinomas of the ovary occurred in the fenretinide group and 10 in the control group. The probability of carrying a BRCA mutation was lower for women with ovarian carcinoma in the treatment arm. Conclusion. Fenretinide treatment was associated with a lower incidence of ovarian carcinoma during the intervention period but such a protective effect seems to disappear after treatment. Furthermore, a possible protective effect of fenretinide in BRCA-mutated women was suggested. Further studies on fenretinide for the prevention of ovarian carcinoma particularly in women with genetic susceptibility appear necessary. (C) 2002 Elsevier Science (USA).