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Journal of the Dermatology Nurses' Association - Featured Journal

February 2010, Volume 2 Number 1 , p 36 - 37

Author

  • Jeff Donovan

Abstract

Von Hoff, D. D., LoRusso, P. M., Rudin, C. M., Reddy, J. C., Yaunch, R. L., Tibes R., et al. (2009). Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. New England Journal of Medicine, 361, 1164-1172.Basal cell carcinoma (BCC) is the most common skin cancer in the United States. Overall, most BCCs are readily curable. Metastatic BCC is uncommon but is associated with poor prognosis. The median survival is 8 months. Molecular studies have shown that many BCCs are associated with gene mutations in a cellular signaling pathway known as the hedgehog signaling pathway. These mutations send signals into cancer cells to instruct them to proliferate. The drug GDC-0449 is a specific inhibitor of one component of the hedgehog pathway.In this study, the authors evaluated the efficacy of GDC-0449 in the treatment of 15 patients with locally advanced BCC and 18 patients with metastatic BCC. Patients were followed for a median of 9.8 months. Of the 33 patients in the study, 18 showed benefit from treatment with GDC-0449. Two of these 18 patients had a complete response, and 16 had a partial response to the drug. Eleven patients did not demonstrate any increase in the size of their tumor during the treatment interval. In 4 patients, the tumor continued to grow despite GDC-0449. The drug was generally well tolerated, although side effects included fatigue (4 patients), hyponatremia (2 patients), muscle spasm (1 patient), and atrial fibrillation (1 patient).REMARK: It has long been recognized that the hedgehog pathway is important in the development of BCC. The oral drug GDC-0449 is an inhibitor of the hedgehog pathway and appears to have antitumor activity against locally advanced and metastatic BCC. Further studies will be helpful to determine how GDC-0449 can best be combined with other therapies to treat advanced disease. Moreover, one wonders whether a topical formulation of GDC-0449 could be designed and used in other less severe forms of BCC. It will be

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