Systemic treatment of advanced cutaneous squamous and basal cell carcinomas

Author
Renato G Martins, MD, MPH Section Editor
Robert S Stern, MD Deputy Editor
Michael E Ross, MD

Last literature review version 17.1: January 2009 | This topic last updated: May 2, 2008 (More)

INTRODUCTION — Basal cell carcinoma and squamous cell carcinoma of the skin, together referred to as nonmelanoma skin cancer, are the most commonly diagnosed malignant neoplasms in thewhite population of the United States. Because many patients are treated as outpatients in an office setting, reliable statistics are difficult to obtain. Nonetheless, the National Cancer Institute estimates that approximately 1 million new cases occurred in 2007 [1] .

The vast majority of patients can be successfully managed with a variety of simple procedures, such as cryotherapy, curettage andelectrodessication, topical treatments (5-fluorouracil, imiquimod), or simple surgical excision. When lesions are more advanced, Mohs micrographic surgery, more extensive surgical resection, or radiation therapy generally are generally sufficient to control locoregional disease.

Despite their high prevalence, these skin cancers are only rarely fatal. It is estimated that in 2007, approximately1000 patients died of the disease. Squamous cell carcinomas are biologically more aggressive, and neglected lesions can be life-threatening both due to local extension or metastasis. In contrast, basal cell carcinoma is only very rarely life threatening.

The use of systemic therapy is limited to patients with distant metastases or locally advanced disease that cannot be adequately managed withsurgical or radiotherapeutic techniques.

Systemic chemotherapy for basal cell and squamous cancers of the skin is discussed here. The treatment of localized basal cell and squamous cell carcinomas are discussed elsewhere. (See "Treatment and prognosis of basal cell carcinoma" and see "Treatment and prognosis of cutaneous squamous cell carcinoma").

SYSTEMIC CHEMOTHERAPY — Because of therarity of metastatic basal cell and squamous cell cancers of the skin, the approach to systemic treatment is based primarily upon isolated case reports, with only a few small case series.

Platinum-based chemotherapy — In the published experience, cisplatin-based combinations appear to be the most active regimens. These regimens were in general adapted from those used for squamous cell cancersarising in other sites.

The potential role of systemic chemotherapy is illustrated by three of the largest reports: A combination of bolus cisplatin, plus a five-day infusion of bleomycin and 5-fluorouracil, was used to treat 14 patients with advanced squamous cell carcinoma of the skin or lip [2] . Objective tumor responses (four complete and seven partial) were observed in 11 patients. In sevenpatients, tumor regression with systemic chemotherapy permitted subsequent definitive local treatment with either surgery or radiation therapy. A case report of one patient with basal cell carcinoma metastatic to the lungs observed a complete response with a combination of carboplatin and paclitaxel [3] . The authors also reviewed the literature and found 12 other patients with metastatic basal cellcarcinoma who were treated with platinum-containing regimens. Among these twelve, five had a complete response and four had a partial response. In another report, five patients with locally advanced disease (three squamous cell and two basal cell) were treated with a combination of cisplatin daily times four plus a four day continuous infusion of bleomycin [4] . Four patients had an objectiveresponse (one complete) and one patient had disease progression.

Other approaches — Although squamous cell and basal cell carcinomas are sensitive to platinum-based chemotherapy, the administration of cisplatin requires adequate kidney function. In addition, cytotoxic chemotherapy can be associated with significant bone marrow toxicity. Patients with these skin cancers often are elderly and...