Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: implications of imatinib mesylate.
OBJECTIVE
To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status.


METHODS
Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or platelet-derived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The anti-tumor effect and safety of Glivec in group B patients were also assessed.


RESULTS
Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant).


CONCLUSIONS
Glivec significantly prolongs the post-recurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients with advanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan, China. ycn@adm.cgmh.org.tw
Chen
Tsung-Wen
TW
Wu
Ting-Jung
TJ
Hsueh
Swei
S
Jan
Yi-Yin
YY
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D005091:Exons / Q000235:genetics; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit