A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis
Jae-Cheol Jo1, Yong Sang Hong, Kyu-Pyo Kim
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
Abstract:
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.
Insights
Sunitinib demonstrated potential antitumor activity in advanced aggressive fibromatosis (AF). It showed efficacy in non-mesenteric AF, but caution is advised for mesenteric cases due to severe adverse events.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Aggressive fibromatosis (AF) is a rare benign tumor with potential for significant morbidity.
- Imatinib has shown some efficacy in AF, possibly through PDGFR-β and KIT pathways.
- Sunitinib, a multi-targeted tyrosine kinase inhibitor, has antiangiogenic properties and targets PDGFRs, KIT, and FLT3.
Purpose of the Study:
- To evaluate the efficacy and safety of sunitinib in patients with advanced aggressive fibromatosis.
- To determine the tumor response rate and survival outcomes in this patient cohort.
Main Methods:
- Prospective, multicenter, uncontrolled study.
- Nineteen patients with advanced AF received sunitinib 37.5 mg/day for 4 weeks per cycle.
- Tumor response assessed by RECIST 1.0 criteria.
Main Results:
- Overall response rate was 26.3% (partial response in 26.3%, stable disease in 42.1%).
- Median follow-up of 20.3 months; 2-year progression-free survival was 74.7%, overall survival was 94.4%.
- Common grade 3/4 adverse events included neutropenia (33.3%), diarrhea (5.3%), and hand-foot syndrome (5.3%).
- Three cases of severe gastrointestinal complications (bleeding, perforation, fistula) occurred in patients with mesenteric AF.
Conclusions:
- Sunitinib exhibits potential antitumor activity in advanced aggressive fibromatosis.
- The drug may be beneficial for non-mesenteric AF.
- Close monitoring for severe adverse events, particularly in mesenteric AF, is crucial.
