Optimizing the dose of imatinib for treatment of gastrointestinal stromal tumours: lessons from the phase 3 trials.
Imatinib therapy for unresectable or metastatic gastrointestinal stromal tumour (GIST) is typically initiated at a dosage of 400mg/d. Two phase 3 studies investigated whether the higher dose of 800 mg/d - administered initially or upon progression on the 400-mg dose - would improve outcomes. Both the studies confirmed the 400mg/d starting dose for most patients. However, two groups benefited from the treatment with 800 mg/d of imatinib: patients with disease progression on standard-dose therapy, and patients whose tumour harbours an exon 9 mutation in KIT. Initial treatment with 800 mg/d of imatinib (400mg BID) should be considered for patients with KIT exon 9-mutant GIST. In unselected patients, dose optimisation to 800 mg/d may be warranted as a first step in managing progressive disease; such patients should be closely monitored.
Patel
Shreyaskumar
S
University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. spatel@mdanderson.org
Zalcberg
John R
JR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009154:Mutation / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha