Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer

• Published in: Journal of clinical oncology Vol. 11; no. 3; p. 474
• Main Authors: Cobleigh, M A, Dowlatshahi, K, Deutsch, T A, Mehta, R G, Moon, R C, Minn, F, Benson, 3rd, A B, Rademaker, A W, Ashenhurst, J B, Wade, 3rd, J L
• Format: Journal Article
• Language: English
• Published: United States 01.03.1993
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Female; Fenretinide - administration & dosage; Fenretinide - adverse effects; Humans; Middle Aged; Tamoxifen - administration & dosage; Treatment Outcome
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1993.11.3.474

Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, previously untreated metastatic breast cancer. Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.