Medical approaches to non-melanoma skin cancer

Abstract

Medical therapy represents an alternative treatment approach that can be considered for some forms of non-melanoma skin cancer (NMSC). In selected cases, topical treatments are preferable to invasive procedures, especially in the case of multifocal lesions, unclear lesion edges, risk of keloids, surgical risk factors and localization in some areas such as the face and décolletage, as the cosmetic outcomes are generally excellent. In the case of advanced and metastatic NMSC, molecularly targeted therapy represents a reasonably promising alternative to classical cytotoxic chemotherapy. Based on the existing literature and the authors’ experience, this paper analyzes and discusses the mechanisms of action, formulations, official and off-label indications, efficacy, side effects and contraindications of medical treatments that are utilized in the treatment of NMSC, including 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, resiquimod, piroxicam, dobesilate, betulinic acid, vismodegib, cetuximab, gefitinib and cytotoxic chemotherapy.

Keywords::

• 5-fluorouracil
• actinic keratosis
• basal cell carcinoma
• cetuximab
• diclofenac
• gefitinib
• imiquimod
• ingenol mebutate
• medical treatment
• skin cancer
• squamous cell carcinoma
• vismodegib

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Medical treatments, both topical and systemic, represent an effective alternative in some forms of skin cancer.

• • Factors that may address topical treatments include extensive, multifocal, multiple tumors, unclear lesion edges, localization in some areas such as the face and décolletage, history of hypertrophic scarring and/or keloids, surgical risk factors (age, associated diseases).

• • Therapeutic response is related to tumor type, extension and localization, and patient compliance. A careful post-treatment follow-up is crucial.

• • The efficacy of topical treatments in actinic keratoses (AKs), Bowen’s disease and small superficial and nodular basal cell carcinomas has a high evidence level.

• • In AKs, the use of some topical agents provides a ‘field effect’ on subclinical disease, and contributes to the prevention of further tumor development in adjacent areas.

• • Local skin reactions of topical treatments vary from mild to severe and patients must be properly advised to enhance compliance.

• • The cosmetic outcomes following topical treatments are generally excellent, especially if compared with those resulting from invasive treatments.

• • Topical 5-fluorouracil has been used the longest in clinical practice and has the best cost–benefit rate.

• • Imiquimod is the most versatile agent, being utilized in several forms of skin cancer; it has strong literature support and sufficient clinical use in most cases.

• • Diclofenac 3% gel in 2.5% hyaluronic acid shows the lowest side effects, but its efficacy is limited to the treatment of AKs.

• • Ingenol mebutate represents the more promising agent for AKs and basal cell carcinomas, both for its efficacy and short course schedule (2–3 days), which should increase patient compliance.

• • As regards the management of locally advanced and metastatic non-melanoma skin cancer, limited information is available, with isolated case reports and small case series.

• • Systemic molecularly targeted therapy with vismodegib and cetuximab represents a promising and reasonable alternative to cytotoxic chemotherapy in locally advanced and metastatic non-melanoma skin cancer.