Response of extraabdominal desmoid tumors to therapy with imatinib mesylate.

BACKGROUND Desmoid tumor represents a rare monoclonal neoplasm arising from deep musculoaponeurotic structures and may occur sporadically or in association with the familial adenomatous polyposis and Gardner syndromes. Desmoid tumors do not appear to demonstrate metastatic potential; however, local infiltrative growth results in significant morbidity and potential mortality. Although the delineation of optimal therapy for desmoid tumors has been confounded by several factors, surgical resection with adjuvant radiotherapy for a positive surgical margin remains the standard approach. Responses have been demonstrated to nonsteroidal antiinflammatory agents, antiestrogen compounds, and a variety of other agents in small series. Imatinib mesylate appears to demonstrate inhibitory activity against multiple class 3 receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, as well as c-kit. METHODS The authors performed immunohistochemical and qualitative real-time polymerase chain reaction analysis on nine desmoid tumor specimens that demonstrated consistent positivity for c-kit as well as PDGFR-alpha and PDGFR-beta. At the time of last follow-up, 2 patients had received therapy with imatinib mesylate at a dose of 400 mg twice daily. RESULTS Both patients demonstrated ongoing radiographic and clinical responses with a duration of 9 months and 11 months, respectively. CONCLUSIONS Imatinib mesylate has been reported to have activity against desmoid tumor, most likely because of c-kit and PDGFR receptor tyrosine kinase activity inhibition, and warrants further study. The relative novelty of this agent and the lack of long-term toxicity data should prompt its use only in the salvage setting in which established local and systemic approaches fail to control disease. In addition, the use of imatinib mesylate in the treatment of this neoplasm preferably should be in the context of a formal prospective clinical trial.