Systemic therapy for inoperable and metastatic basal cell cancer

Abstract

Cutaneous basal cell carcinoma (BCC) is the most common human malignancy. The majority of cases are cured with local therapies and advanced disease is quite rare. However, locally advanced (inoperable) and metastatic basal cell carcinoma may occur more often than previously thought. Surgery, and other local therapies, is the primary treatment for BCC. However, some resections can be extensive and carry significant morbidity or disfigurement. The prognosis for locally advanced and metastatic BCC is quite poor, and cytotoxic chemotherapies offer limited benefit. Aberrations in the sonic hedgehog (HH) signaling pathway are common in BCC. Novel molecular therapies targeted against this pathway, such as vismodegib (GDC-0449), have shown dramatic activity in advanced basal cell carcinoma. The role of these in nevoid basal cell carcinoma syndrome (Gorlin) syndrome is still under investigation. However, systemic therapies are not curative and require long-term treatment and should not be used in place of curative procedures. Evaluation by experienced physicians and/or by a multidisciplinary tumor board for possible curative/definitive surgery with or without radiation is recommended before initiation of systemic therapy. Clinical trial enrollment also is recommended. Comorbid conditions as well as social circumstances may be factors when deciding on an optimal therapy, in particular with oral agents. Patients treated with HH pathway inhibitors require regular physician monitoring to assess for side effects, benefit, and compliance. Patients of child-bearing potential must be strongly counseled regarding the risk of birth defects and need for birth control. Primary and secondary resistance to HH pathway inhibitors is only beginning to be described.