title: Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced GIST: preliminary experience from Chang Gung Memorial Hospital.
abstract: OBJECTIVE
  Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutation of kit or platelet-derived growth factor receptor alpha (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese with advanced GIST treated with imatinib were reported.
  
  
  METHODS
  Between 2001 and May 2006, a prospective, non-randomized, and a single center trial containing 64 Taiwanese patients with advanced GIST treated with imatinib was conducted. Each tumor was investigated for mutations of kit or PDGFRA.
  
  
  RESULTS
  The median follow-up time after imatinib administration was 16.1 months. 12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64 Taiwanese with advanced GIST had an estimated median survival of 48.0 months and 4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test patients and five of them had no mutation (9.3%). No PDGFRA mutant was identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0% (not significant; P = 0.149).
  
  
  CONCLUSIONS
  Activated mutation of kit constituted 90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation was detected. Imatinib induced a sustained objective response in more than half of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs had no mutation, kit exon 9, and 11 mutations.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan. ycn@adm.cgmh.org.tw
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.forename: Tsung-Wen
authors.initials: TW
authors.lastname: Chen
authors.forename: Hsiang-Lin
authors.initials: HL
authors.lastname: Lee
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Liu
authors.forename: Tzu-Chieh
authors.initials: TC
authors.lastname: Chao
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004273:DNA, Neoplasm; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha