title: Imatinib escalation or sunitinib treatment after first-line imatinib in metastatic gastrointestinal stromal tumor patients.
abstract: OBJECTIVE
  Imatinib mesylate (IM) is effective in metastatic gastrointestinal stromal tumor (GIST) patients; however, disease progression eventually occurs due to IM resistance or intolerance. Treatment options include IM escalation or a direct shift to sunitinib, but comparison of these strategies is required.
  
  
  METHODS
  This study included 91 out of 214 metastatic GIST patients treated with IM, who experienced progression or intolerance between August 2001 and December 2012 at the Chang Gung Memorial Hospital. Treatment efficacy and safety profiles were retrospectively compared between groups of patients who either received escalated IM or were directly switched to sunitinib.
  
  
  RESULTS
  There were no significant differences in age, gender, second-line treatment causes or gene mutations in the IM escalation group (N=63) versus the sunitinib group (N=28). The 2 groups had similar progression-free survival (PFS, p=0.316) and overall survival (OS, p=0.599). Patients without primary KIT exon 9 mutations and who treated with sunitinib had significantly better PFS (14.3 vs. 6.2 months, p=0.037) and a trend toward better OS (not reached vs. 16.4 months, p=0.161) compared to the IM-escalation group. Patients in both groups with responses and stable disease (SD), and IM escalation patients who underwent surgery and who had KIT exon 9 mutations, had favorable PFS. The most common non-hematological adverse events were edema in the IM escalation group and hand-foot syndrome and hypertension in the sunitinib group.
  
  
  CONCLUSIONS
  Comparable results were achieved by IM escalation and sunitinib treatment. Physicians should consider kinase mutations and specific adverse effects when choosing between these treatments.
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Chiao-En
authors.initials: CE
authors.lastname: Wu
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Radiology, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Jeng-Hwei
authors.initials: JH
authors.lastname: Tseng
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Chi-Tung
authors.initials: CT
authors.lastname: Cheng
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Tsung-Wen
authors.initials: TW
authors.lastname: Chen
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan, R.O.C. chen.y9964@gmail.com yehchunnan@gmail.com.
authors.forename: Yen-Yang
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Gastrointestinal Stromal Tumor Team, Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, R.O.C. chen.y9964@gmail.com yehchunnan@gmail.com.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib
keywords: Gastrointestinal stromal tumor; imatinib mesylate; second-line therapy; sunitinib