A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis.

Several studies have reported that imatinib may induce tumor responses and prolonged disease stabilization in aggressive fibromatosis (AF). This effect may relate to the PDGFR-β pathway and KIT mutations. Sunitinib not only inhibits PDGFRs, KIT, and FLT3, it also blocks VEGFRs and thus serves as an antiangiogenic agent. The aim of this prospective multicenter uncontrolled study was to evaluate the efficacy and safety of sunitinib in patients with advanced AF. Nineteen patients with pathologically proven AF were recruited between June, 2008, and March, 2012, from three centers. One treatment cycle consisted of 37.5 mg/day sunitinib for 4 weeks without a break. The primary endpoint was tumor response rate according to RECIST 1.0. Ten (53 %) patients were female and the median age was 30 years (range, 22-67). Most of the primary sites were intra-abdominal (12, 63.2 %), and AF associated with familial adenomatous polyposis in ten patients (52.6 %). With a median of six cycles per patients (range, 1-47 cycles), five patients (26.3 %) achieved a partial response and eight (42.1 %) had stable disease. The overall response rate was 26.3 % (95 % confidence interval [CI], 6.3-45.7) in intention-to-treat analysis. With a median follow-up time of 20.3 months (range, 1.8-50.7), the 2-year rates of progression-free and overall survival were 74.7 % and 94.4 %, respectively. Grade 3 or 4 adverse events of sunitinib that occurred in >5 % of patients were neutropenia (33.3 %), diarrhea (5.3 %), and hand-foot syndrome (5.3 %). In 3 of 12 patients with mesenteric AF, mesenteric mass bleeding (n = 1), bowel perforation (n = 1), and bowel fistula (n = 1) with tumor mass necrosis were observed early during sunitinib treatment. Therefore, sunitinib showed potential antitumor activity and may be useful for the management of non-mesenteric AF.