Summary
Retinoids, the natural and synthetic analogs of vitamin A, are growth-inhibiting and differentiation-inducing agents and show clinical promise as chemopreventive and antineoplastic agents. Fenretinide, a new synthetic retinoid, has antitumor activity in certain in vitro and in vivo model systems and was relatively nontoxic in phase I trials. Based on these data, we designed a phase II study of Fenretinide involving 31 patients with advanced breast cancer [15] and melanoma [16], two cancers shown to be responsive to this agent in preclinical models. Fenretinide was inactive in patients with advanced disease. Toxicity was mild, and reversible. Mucocutaneous side effects occurred in 16 (52%) patients. Nyctalopia developed in three patients one of whom developed decreased B-wave amplitude of the scotopic electroretinogram. The minimal toxicity and significant activity in preclinical studies make this an attractive agent for future breast cancer chemoprevention studies.
Similar content being viewed by others
References
Lippman SM, Kassler JF, Meyskens FL: Retinoids as preventive and therapeutic anticancer agents. Cancer Treat Rep 71: 391–405 (Part I), 493–515 (Part II), 1987
Ratko TA, Detrisac CJ, Dinger NM, Thomas CF, Kelloff GJ, Moon RC: Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats. Cancer Res 49: 4472–4476, 1989
Dowlatshahi K, Mehta RG, Thomas CF, Dinger NM, Moon RC: Therapeutic effect of N-[4-hydroxyphenyl]retinamide on N-methyl-N-nitrosourea induced rat mammary cancer. Cancer Letters, in press, 1989
Costa A, Malone W, Perloff M, Buranelli F, Campa T, Dossena G, Magni A, Pizzichetta A, Andreoli C, Del Vecchio M, Formelli F, Barbieri A: Tolerability of the synthetic retinoid fenretinide (HPR). Eur J Cancer Clin Oncol 25: 805–808, 1989
Kaiser-Kupfer MI, Peck GL, Caruso RC, Jaffe MJ, DiGiovanna JJ, Gross EG: Abnormal retinal function associated with fenretinide, a synthetic retinoid. Arch Ophthalmol 104: 69–70, 1986
Peng Y-M, Dalton WS, Alberts DS, Xu M-J, Lim H, Meyskens FL: Pharmacokinetics of N-4-hydroxyphenyl-retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients. Eur J Cancer 43: 22–26, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Modiano, M.R., Dalton, W.S., Lippman, S.M. et al. Phase II study of Fenretinide (N-[4-Hydroxyphenyl]retinamide) in advanced breast cancer and melanoma. Invest New Drugs 8, 317–319 (1990). https://doi.org/10.1007/BF00171846
Issue Date:
DOI: https://doi.org/10.1007/BF00171846