Pharmacologic treatment options for advanced epithelial skin cancer

Epithelial skin cancers (ESCs), namely basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are considered common skin malignancies, with rising incidence rates over the past few decades. A subgroup of patients with ESC present with advanced and 'difficult'-to-treat tumours, including locally advanced and metastatic tumours. Currently, there is no widely accepted staging system for locally advanced ESCs, while metastatic BCCs and SCCs share a staging system. Therefore, selecting an appropriate therapeutic regimen for these patients may be difficult.

The purpose of this review is to highlight the pharmacologic treatment options for advanced ESCs. These include 'conventional' chemotherapeutic regimens such as 5-fluorouracil, cisplatin, vincristine, bleomycin and doxorubicin and newer, more 'targeted' therapies.

Vismodegib, a Hedgehog (Hh) inhibitor, was recently approved for the treatment of advanced BCC showing a good efficacy rate and a relatively well-tolerated safety profile in clinical studies. In addition, a number of hedgehog inhibitors are now in Phase I and II trials of advanced BCC demonstrating encouraging results. Phase II studies with epithelial growth factor receptor inhibitors, such as cetuximab, gefitinib, panitimumab and erlotinib have been conducted in patients with advanced SCCs, used either as monotherapy or in combination with chemotherapy. However, there is still much knowledge to be gained about the treatment efficacies, optimal treatment durations, mechanisms of drug tolerance, adverse events and the ways in which these therapies influence patient outcomes and quality of life.