title: [Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor].
abstract: OBJECTIVE
  To investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.
  
  
  METHODS
  Clinical data of 48 patients with imatinib-resistant GIST received sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian Medical University were analyzed retrospectively. Eighteen patients received 50 mg/d of sunitinib in a protocol of 4/2 (4 weeks on and 2 weeks off) [50 mg/d (4/2)], and 30 patients received a protocol of 37.5 mg of sunitinib continuous daily dose (37.5 mg/d CDD).
  
  
  RESULTS
  The median duration of sunitinib administration of all the 48 patients was 56 weeks, and the short-term efficacy was evaluated at 24 weeks after the initial treatment according to the Choi criteria. The response rate was 27.1% (13/48), including 1 case with complete response (CR), 12 cases with partial response (PR), and 21 cases with stationary disease (SD). The disease control rate was 70.8% (34/48). The mean follow-up time of 48 patients was 89 weeks. The median progression-free survival (PFS) and overall survival (OS) were 48 weeks and 92 weeks respectively. Stratified analyses indicated that the median PFS of patients previously treated by imatinib 400 mg/d and >400 mg/d were 53 weeks and 35 weeks respectively (P=0.018), and the median OS of these two groups were 157 weeks and 71 weeks respectively (P=0.003). Patients with exon 11 mutations had a significantly shorter OS compared with those with exon 9 mutations (71 weeks vs 157 weeks, P=0.008). Hand-foot syndrome was the most common adverse effect (25/48, 52.1%), followed by nausea (24/48, 50.0%), fatigue (23/48, 47.9%), neutropenia(21/48, 41.7%). The sub-group analysis of two protocols of sunitinib administration showed that the incidence of diarrhea and hand-foot syndrome were higher in 50 mg/d (4/2) group than those in 37.5 mg/d CDD group (P=0.027, P=0.048).
  
  
  CONCLUSIONS
  Sunitinib is effective for the patients with imatinib-resistant GIST. After 400 mg/d imatinib treatment failure, sunitinib should be prescribed instead of increased dosage of imatinib. Patients with KIT exon 9 mutations present better prognosis than those with KIT exon 11 mutations. The protocol of sunitinib 37.5 mg/d CDD possesses better safety.
authors.affiliation: Department of Gastrointestinal Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, China. liu9503@126.com
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Wei-zhong
authors.initials: WZ
authors.lastname: Jiang
authors.forename: Guo-xian
authors.initials: GX
authors.lastname: Guan
authors.forename: Zhi-fen
authors.initials: ZF
authors.lastname: Chen
authors.forename: Pan
authors.initials: P
authors.lastname: Chi
authors.forename: Hui-shan
authors.initials: HS
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D000077210:Sunitinib