Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment.
OBJECTIVE
Imatinib mesylate showed a sustained objective response in patients with advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001. Here we reported genetic changes during imatinib mesylate treatment especially when the patient had partial response or stationary disease.


METHODS
Between 2001 and June 2005, 44 advanced GIST patients were treated with imatinib mesylate. Among them, five patients (11.9%) (four with partial response and one with stationary disease) received surgical treatment during imatinib mesylate treatment. We compared the genetic status of each tumor in the five patients before and after imatinib mesylate treatment.


RESULTS
Symptomatic gallbladder stone with or without cholecystitis (two patients), lower GI bleeding (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one patient) comprised the indications for operation. Before imatinib mesylate treatment, four of the five patients displayed deletion mutation and one patient displayed point mutation in exon 11. After treatment, one patient developed second novel missense mutation in exon 17 with acquired resistance since he was administered with only half dose of imatinib mesylate. The other four patients taking the same dose of imatinib mesylate exhibited identical mutation to the previous lesions.


CONCLUSIONS
Necrosis of large and bulky tumors after imatinib mesylate therapy might be the reason of gastrointestinal hemorrhage and enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could induce acquired resistance during treatment and second novel mutation might be the reason.
Yeh
Chun-Nan
CN
Department of Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan, ycn@adm.cgmh.org.tw
Chen
Tsung-Wen
TW
Liu
Feng-Yuan
FY
Jan
Yi-Yin
YY
Chen
Miin-Fu
MF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit