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David S. Hong, MD; Srini B. Reddy, MD; Victor G. Prieto, MD; John J. Wright, MD, PhD; Nizar M. Tannir, MD; Philip R. Cohen, MD; A. Hafeez Diwan, MD, PhD; Harry L. Evans, MD; Razelle Kurzrock, MD

Arch Dermatol. 2008;144(6):779-782.

Background  Keratoacanthomas, as well as an actinic keratosis progressing to squamous cell cancer, have been reported in patients who were treated with sorafenib, a multikinase inhibitor known to suppress the actions of Raf kinase and vascular endothelial growth factor receptor.

Observations  We describe a 70-year-old white woman with metastatic renal cell carcinoma who was treated with a combination of sorafenib and tipifarnib (a farnesyltransferase inhibitor). She had no history of skin cancer. However, within 3 months after starting this therapy, she developed 3 erythematous nodules on her legs. Pathologic examination showed deeply invasive, well-differentiated squamous cell carcinomas. The tumors were excised, and sorafenib-tipifarnib treatment was discontinued. No new lesions have developed to date.

Conclusions  Targeted agents, such as sorafenib and tipifarnib, are increasingly being used in the management of visceral malignant neoplasms. A temporal relationship was observed between the initiation of the targeted treatments and the emergence of these cutaneous cancers. Further study of the mechanisms responsible for the rapid appearance of squamous cell cancers in this setting may provide insights into the pathogenesis of skin tumors.

Author Affiliations: Phase I Program, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine (Drs Hong, Reddy, and Kurzrock), and Departments of Pathology (Drs Prieto, Diwan, and Evans), Dermatology (Drs Prieto and Diwan), and Genitourinary Medical Oncology (Dr Tannir), University of Texas M. D. Anderson Cancer Center, Houston; National Cancer Institute, Bethesda, Maryland (Dr Wright); and Departments of Dermatology, University of Houston Health Center (Dr Cohen) and University of Texas–Houston Medical School (Dr Cohen).

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