Investigational New Drugs

, Volume 32, Issue 2, pp 369–376 | Cite as

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

  • Jae-Cheol Jo
  • Yong Sang Hong
  • Kyu-Pyo Kim
  • Jae-Lyun Lee
  • Jeeyun Lee
  • Young Suk Park
  • Sun Young Kim
  • Jin-Sook Ryu
  • Jong-Seok Lee
  • Tae Won KimEmail author


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.


Aggressive fibromatosis Desmoid tumor Phase II Sunitinib 



Sunitinib was kindly provided by Pfizer Korea. This study was supported by grants from the Korea Health 21 R&D Project, Ministry of Health & Welfare and Family Affairs, Republic of Korea (A062254 and A070001). This clinical trial was presented in part at the ESMO 2012 congress, Vienna, Austria, 28 September to 2 October, 2012.

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jae-Cheol Jo
    • 1
    • 6
  • Yong Sang Hong
    • 1
  • Kyu-Pyo Kim
    • 1
  • Jae-Lyun Lee
    • 1
  • Jeeyun Lee
    • 2
  • Young Suk Park
    • 2
  • Sun Young Kim
    • 3
  • Jin-Sook Ryu
    • 4
  • Jong-Seok Lee
    • 5
  • Tae Won Kim
    • 1
    Email author
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  3. 3.Center for Colorectal CancerNational Cancer CenterGoyangKorea
  4. 4.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of Orthopedics, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  6. 6.Department of Hematology and Oncology, Ulsan University HospitalUniversity of Ulsan College of MedicineUlsanKorea

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