Oral therapy for nonmelanoma skin cancer in patients with advanced disease and large tumor burden: a review of the literature with focus on a new generation of targeted therapies.

Nonmelanoma skin cancer (NMSC) is the most common cancer in patients and includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Treatments useful for SCC and BCC include surgical, topical, and in advanced cases systemic chemo-radiation. This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. Oral tyrosine kinase inhibitors Erlotinib and Gefitinib, which target epidermal growth factor receptor (EGFR), have early supporting data and are currently undergoing large multicenter trials. Other less studied oral therapies which have shown at least partial efficacy include 5-Fluorouracil, capecitabine, and picropodophyllin. In vitro studies have elucidated new targets for dual combination oral therapy targeting both EGFR and insulin-like growth factor 1 receptor (IGF-1R). It is important to stratify treatment options based on patient risk of advanced disease, failure of conservative treatment, and ill-tolerated intravenous chemotherapy adverse events. Oral therapy in NMSC is useful in high risk patients with recurrent and aggressive disease who may not tolerate other systemic therapies.