Continuing medical education
Topical pharmacotherapy for skin cancer: Part I. Pharmacology

https://doi.org/10.1016/j.jaad.2013.12.045Get rights and content

Topical pharmacotherapy represents an effective alternative treatment for superficial skin cancer, primarily actinic keratoses and basal cell carcinomas. We provide an in-depth analysis of the pharmacologic aspects of available topical drugs for the treatment of primary skin tumors. In particular, we evaluate the mechanisms of action, formulations and indications, side effects, and contraindications of 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, and retinoids. Moreover, the characteristics of some investigational molecules (ie, resiquimod, piroxicam, dobesilate, and betulinic acid) are presented.

Introduction

Since the introduction of 5-fluorouracil in the 1960s,1 a number of topical drugs have been used for the treatment of skin tumors. Some of these topical drugs have been approved by the US Food and Drug Administration for selected indications; others are used off-label or are under investigation.

The purpose of this review is to provide an in-depth analysis of the available topical treatments for primary skin cancers (Table I), including their mechanism of action, formulations, indications, side effects, and contraindications. The effectiveness of these drugs in the treatment of skin cancer, according to evidence-based medicine guidelines, is evaluated in part II of this continuing medical education article.

Section snippets

5-Fluoruracil

Key points

  1. 5-Fluorouracil acts as an antimetabolite, interfering with DNA synthesis

  2. Topical 0.5%, 1%, 2%, and 5% 5-fluorouracil are approved by the US Food and Drug Administration for the treatment of actinic keratoses

  3. The 5% formulation is also approved by the US Food and Drug Administration for the treatment of superficial basal cell carcinomas

  4. The most common local skin reactions observed during treatment with 5-fluorouracil include erythema, blistering, necrosis, and erosions, accompanied by pruritus and

Imiquimod

Key points

  1. Imiquimod is a synthetic immune response modifier

  2. Imiquimod 5%, 3.75%, and 2.5% cream are approved by the US Food and Drug Administration for face and scalp actinic keratoses

  3. Imiquimod 5% is also approved by the US Food and Drug Administration for the treatment of superficial basal cell carcinomas

  4. Patients treated with imiquimod may experience moderate to severe local skin reactions, occasionally extending beyond the application site, including pruritus, burning, erythema, vesicles, erosions,

Diclofenac

Key points

  1. Diclofenac acts by downregulating cyclooxygenase enzymes and increasing apoptosis

  2. A unique topical formulation containing diclofenac 3% gel in 2.5% hyaluronic acid is approved by the US Food and Drug Administration for the treatment of actinic keratoses

  3. Diclofenac 3% gel in 2.5% hyaluronic acid is considered a well-tolerated treatment, with mild irritant side effects at application sites

Diclofenac is a potent nonsteroidal antiinflammatory drug (NSAID).

Ingenol mebutate

Key points

  1. Ingenol mebutate has a dual mechanism of action: the induction of rapid cellular death (within a few hours) followed by an inflammatory response (within days)

  2. Two formulations of ingenol mebutate are available and approved by the US Food and Drug Administration for the treatment of actinic keratoses: a 0.015% gel for the face and scalp lesions once daily for 3 days and a 0.05% gel for the trunk and extremities once daily for 2 days

  3. The most common local skin reactions related to the use of

Retinoids

Key points

  1. Retinoids interfere with cell proliferation and differentiation through their interaction with specific cellular and nuclear receptors

  2. Topical retinoids used off-label in the treatment of skin cancer include tretinoin, isotretinoin, adapalene, and tazarotene

  3. Topical retinoids may be responsible for mild to moderate local side effects, including erythema, peeling, dryness, burning, and pruritus

Retinoids include a variety of vitamin A (retinol) derivatives that are commercially available for the

Emerging therapies

Key points

  1. Resiquimod is an immune response modifier investigated for the topical treatment of actinic keratoses

  2. Piroxicam, a NSAID that inhibits the activity of COX-1 and COX-2, is being evaluated as a possible agent in the treatment of actinic keratoses

  3. Topical experimental formulations containing calcium dobesilate 2.5% and potassium dobesilate 5% have been utilized for the treatment of basal cell carcinomas and actinic keratoses

  4. Betulinic acid is a natural compound that exerts cytotoxic,

Conclusions

Several topical drugs are now available for the treatment of superficial forms of skin cancer. New molecules are under development, as are new formulations, new dosages and simpler therapeutic schedule of existing agents, which may ensure greater patient compliance.

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    Conflicts of interest: None declared.

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