Antiangiogenic treatment of mesenteric desmoid tumors with toremifene and interferon alfa-2b: Report of two cases

PURPOSE: Desmoid tumors are uncommon, benign, fibrous lesions occurring sporadically and in association with familial adenomatous polyposis. Typical clinical features include a locally aggressive behavior, an unpredictable course, and a high propensity for recurrence after surgical resection. There are no standard medical or surgical approaches, and no markers for monitoring medical therapy of desmoid tumors. METHODS: We report two cases of mesenteric desmoid tumors treated with interferon alfa-2b and toremifene, a novel regimen devised to block angiogenesis. Pre- and posttreatment desmoid tumor tissues were obtained in one patient during a repeat resection for recurrent stenosing Crohn's disease and examined for mean vessel count and cellular proliferation levels by immunostaining for the endothelial surface antigen CD31 and the proliferation associated nuclear antigen, Ki-67, respectively. We assessed plasma D-dimers, a potential marker of angiogenic activity, and followed this throughout the course of antiangiogenic therapy in our two patients. RESULTS: Examination of posttreatment tissue revealed a significant decrease in microvessel density (P < 0.02) and Ki-67-positive nuclei (P < 0.0001) compared with pretreatment tissue. Both patients demonstrated a prompt and sustained drop in previously elevated plasma D-dimer levels, which correlated clinically with lesion regression and sustained remission. CONCLUSIONS: Treatment with toremifene and interferon alfa-2b was successful and well tolerated in our two patients. Our data suggest a combined antiangiogenic and antiproliferative mechanism of action. Furthermore, normalization of previously elevated plasma D-dimers may emerge as a strategy to monitor treatment efficacy in mesenteric desmoid tumors.