VIENNA — Imatinib, a protein-tyrosine kinase inhibitor indicated for chronic myeloid leukemia and certain stages of gastrointestinal stromal tumors, has shown clinical activity against dermatofibrosarcoma protuberans, Jens Gille, M.D., reported at the 10th World Congress on Cancers of the Skin.
DFSP, a rare and locally aggressive cutaneous tumor, is typically treated with wide surgical excision. Imatinib (Gleevec) could be used to improve the effectiveness of surgery or as an alternative treatment for unresectable DFSP, said Dr. Gille of Johann Wolfgang Goethe University in Frankfurt, Germany.
In a study of 10 people with DFSP, imatinib 400 mg twice daily resulted in a complete clinical response in four patients with locally advanced disease and a partial response in four patients with local disease and in one with metastatic disease (J. Clin. Oncol. 2005;23:866–73).
DFSP is often associated with a translocation between chromosomes 17 and 22. No clinical response was seen in one patient with metastatic disease whose tumor lacked this translocation, suggesting that variants of DFSP without the translocation may not respond to imatinib.
Imatinib, other tyrosine kinase inhibitors, and T4 endonuclease V are among the promising therapeutic avenues being pursued for nonmelanoma skin cancer. The epidermal growth factor receptor tyrosine kinase inhibitors, gefitinib (Iressa) and erlotinib (Tarceva), are approved for advanced non-small cell lung cancers, and have potential for squamous cell carcinomas of the skin, he said.
Two phase II trials of gefitinib are underway in patients with squamous cell carcinoma and topical therapies on the horizon include T4 endonuclease V, a bacterial DNA repair enzyme that increases the rate of repair of sunlight-induced DNA damage in human cells, Dr. Gille said at the congress cosponsored by the Skin Cancer Foundation.
Dr. Gille also noted that the effectiveness of cyclooxygenase-2 inhibitors in nonmelanoma skin cancer remains to be determined. Two skin trials were halted in 2005 after concerns were raised about the safety of several COX-2 inhibitors.
The trials were evaluating the effectiveness of celecoxib (Celebrex) in 60 patients with basal cell nevi and in 240 patients with sun-damaged skin. Analyses of the available data from both trials could be out later this year, he said.