Chemoprevention of breast cancer with retinoids.
Fenretinide [N-(4-hydroxyphenyl)retinamide, 4-HPR] is an effective agent for the inhibition of N-nitroso-N-methylurea-induced breast cancer in rats. This compound has been studied extensively and proved to be safer and less teratogenic than many other retinoids. A major characteristic of 4-HPR is its ability to concentrate in the granular and fat tissue of the breast instead of in the liver. Between January and June 1986, we carried out a phase I study on 101 patients divided into four randomized groups receiving placebo and 100, 200, and 300 mg/day of 4-HPR. Patients received the drug for 6 months without any major toxic effect. This finding was confirmed by another 6-month study in which patients received a common dose of 200 mg/day. In March 1987, a phase III study was started to evaluate the effectiveness of 4-HPR in preventing contralateral primary tumors in women who had already been treated for breast cancer. If 4-HPR succeeds in preventing second primaries in breast cancer patients, it may be useful for a wider group of subjects at high risk for breast cancer. This randomized study was designed with two arms: an intervention group versus a group receiving no treatment. Patients in the intervention group will be treated with 200 mg/day 4-HPR for 5 years. Patients in the control group will not be treated. A further 2 years of follow-up is planned for both groups. Currently, 2450 patients have been recruited. We expect a total accrual of 3500 patients by the end of 1992.
Veronesi
U
U
Istituto Nazionale Tumori, Milan, Italy.
De Palo
G
G
Costa
A
A
Formelli
F
F
Marubini
E
E
Del Vecchio
M
M
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000517:prevention & control*; D004341:Drug Evaluation; D005260:Female; D017313:Fenretinide; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D017313:Fenretinide; D014212:Tretinoin