title: The role of high-dose imatinib in the management of patients with gastrointestinal stromal tumor.
abstract: After an era of few treatment options for patients with locally advanced or metastatic gastrointestinal stromal tumor (GIST), imatinib has emerged as the standard of care and first-line treatment for these patients. Although imatinib was initially approved at the doses of 400 and 600 mg daily, results from clinical studies established 400 mg daily as the standard initial dose for the majority of advanced GIST patients. Nevertheless, the use of high-dose imatinib (800 mg daily) has been shown to benefit patients with advanced or metastatic GIST that progresses on the standard-dose, and has been recommended in this setting by the major management guidelines in Europe and the United States. Results from the Meta-GIST meta-analysis showed that patients whose GIST harbors a KIT exon 9 mutation garner a longer progression-free survival time when treated initially with high-dose imatinib (800 mg daily) compared with those patients with KIT exon 11 or no mutations. Thus, the use of high-dose imatinib is recommended by the clinical practice guidelines in these 2 specific clinical situations. In addition, clinicians should weigh the clinical benefit of administering high-dose imatinib against the associated toxicities, as well as the proper management of dose-related side effects.
authors.affiliation: Department of Surgery, National Institute for the Study of a Cure for Tumors, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trent
mesh_terms: D001549:Benzamides; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D009154:Mutation; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate