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.
