A Review of the Chemopreventative Effects of Oral Retinoids for Internal Neoplasms

November 2011 | Volume 10 | Issue 11 | Original Article | 1292 | Copyright © 2011

Tina Bhutani MD and John Koo MD

Abstract

With the recent data showing that psoriasis patients are at higher risk for systemic malignancies, there is a growing awareness for the need to minimize cancer risks in psoriasis patients. Retinoids as a class of medication have been widely studied as potential agents for cancer chemoprevention. Since they act by inducing cell differentiation and maturation, they may help reverse the pathogenesis of malignancies. Through an extensive literature review, this paper provides an update on the available data on retinoids and their systemic anti-cancer properties. Retinoids appear to be beneficial in the prevention of cutaneous T-cell lymphoma, acute promyelocytic leukemia, head and neck cancers, hepatocellular carcinoma, breast cancer and neuroblastoma. So far the data does not support anti-cancer efficacy of retinoids in the prevention of prostate or pancreatic cancer and may possibly have harmful effects in the pathogenesis of lung cancer in smokers.

J Drugs Dermatol. 2011;10(11):1292-1298.

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INTRODUCTION

Recent population-based studies have suggested that patients with psoriasis are at higher risk for development of systemic malignancies.1 In addition, other than oral retinoids, all systemic therapy used to treat psoriasis are immunosuppressants, including methotrexate, cyclosporines, and the biologics, which, at least theoretically, can put patients at even greater risk of developing cancer.2 Therefore, with the recent expanding use of these agents, the risk of systemic malignancies is a growing concern in the systemic treatment of psoriasis.

Cancer chemoprevention is a concept that was first developed by Sporn in the late 1970s and is defined as the use of natural, synthetic or biologic chemical agents for reversing, suppressing or preventing carcinogenic progression.3,4 Interestingly, retinoids as a class of medications have been widely studied as agents for cancer chemoprevention. Natural (retinol, beta-carotene) and synthetic (fenretinide, etretinate, isotretinoin, acitretin, all-trans retinoic acid) retinoids have all been shown to induce cell differentiation and maturation, modulate growth, and induce apoptosis in various cell lines and animal models.5,6This makes retinoids a potential candidate for use in chemoprevention given that the abnormal growth in cancers is, in part, due to a lack of differentiation and maturation that could be reversed by this class of medications. In fact, dermatologists have long been aware of the anti-cancer effects of retinoids on nonmelanoma skin cancer as evidenced by the multitude of literature on this topic.7-11 However, the chemopreventative effects of oral retinoids for systemic malignancies are not as well known among practicing dermatologists and hence will be the topic of this review.

METHODS

A literature search for cohort studies, clinical trials, randomized control trials and review articles between 1984 and 2009 was performed. The keyword retinoid was combined with malignancy, neoplasm, cancer, chemoprevention, and chemotherapy. The search yielded over 8,000 articles, of which 66 were chosen for this review. The focus of the search included the use of retinoids in the prevention of internal malignancies including hematologic malignancies, oral leukoplakia, head and neck cancer, hepatocellular carcinoma, cervical cancer, breast cancer, neuroblastoma, prostate cancer, and pancreatic cancer. Due to the large amount of information on these topics, the largest scale clinical trials were reviewed, which demonstrated or failed to demonstrate efficacy of retinoids in cancer.

RESULTS

Malignancies for Which Retinoids Are Most Likely Helpful

Hematologic Malignancy
Cutaneous T-Cell Lymphoma (CTCL)
Primary CTCL defines a group of primary cutaneous lymphoma of which mycosis fungoides and Sezary syndrome are the most common.12 The incidence of CTCL in the United States is increasing; the overall incidence is 6.4 per million persons with a higher incidence in male patients and older age groups.13

Bexarotene (Targretin) is a synthetic retinoid analogue formally approved for the treatment of CTCL that is refractory to at least one systemic medication. A recent phase 2/3, multicenter, open-label trial randomized 58 patients with refractory

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