Optimizing the dose of imatinib for treatment of gastrointestinal stromal tumours: lessons from the phase 3 trials

Eur J Cancer. 2008 Mar;44(4):501-9. doi: 10.1016/j.ejca.2007.11.021. Epub 2008 Jan 29.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Benzamides
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / mortality
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Mutation / genetics
  • Piperazines / administration & dosage*
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / administration & dosage*
  • Randomized Controlled Trials as Topic
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha