An Overview of Cytotoxic Chemotherapy, Immunotherapy, and Targeted Therapy for Advanced Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is the second most common type of non-melanoma skin cancer after basal cell carcinoma, and its incidence is continuously increasing. Although most cutaneous SCCs are localized early-stage tumors, regional lymph node and distant metastases can occasionally develop. The standard treatment of early disease is surgical excision, and shows good prognosis. In contrast, the treatment of advanced disease, such as unresectable or metastatic disease, is difficult, and there are currently no established standard treatment options, despite it being a potentially life-threatening condition. In the past, the clinical outcomes of various regimens have been investigated, including bleomycin, peplomycin, platinum agents, anthracycline agents, fluoropyrimidines, 13-cis-retinoic acid, and interferon-2a. Several clinical trials have shown favorable responses to these agents; however, these were all limited by a lack of randomization, a small number of enrolled patients, and/or heterogeneous patient populations, resulting in a lack of defined treatment strategies for this disease.

Recent studies have elucidated that the epidermal growth factor receptor (EGFR) is highly expressed in many epithelial tumors, including non-cutaneous SCC of the head and neck and cutaneous SCC, and several agents that target human EGFR, such as gefitinib, cetuximab, and erlotinib, have shown preliminary evidence of activity in phase II clinical trials and case series reports.

This review looks mainly at the previously published clinical trials in an attempt to assess the effectiveness of the various modalities used in the treatment of advanced cutaneous SCC, and aims to provide an overview of the current evidence base and to highlight the areas in need of further research. Only appropriate clinical trials that are well randomized and include adequate patient numbers with well-defined endpoints may prove the clinical efficacy of these promising treatment options.

Keywords: Chemotherapy, Cutaneous squamous cell carcinoma, Cytotoxic agents, Human epidermal growth factor receptor, Immunotherapy, Interferon-α, Retinoids, Targeted therapy.