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
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
