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

M. A. Cobleigh*, K. Dowlatshahi, T. A. Deutsch, R. G. Mehta, R. C. Moon, F. Minn, A. B. Benson, A. W. Rademaker, J. B. Ashenhurst, J. L. Wade, J. Wolter

*Corresponding author for this work

Research output: Contribution to journalArticle

70 Scopus citations


Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.

Original languageEnglish (US)
Pages (from-to)474-477
Number of pages4
JournalJournal of Clinical Oncology
Issue number3
StatePublished - Jan 1 1993


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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