Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

World J Gastroenterol. 2012 Feb 21;18(7):698-703. doi: 10.3748/wjg.v18.i7.698.

Abstract

Aim: To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).

Methods: Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study. Patients received imatinib with dose escalation to 600 mg/d, and further dose escalation to 800 mg/d if imatinib 600 mg/d failed. Progression-free survival, overall survival, clinical efficacy, c-kit/PDGFRA genotype and safety were evaluated.

Results: 52 patients were enrolled in this study. For the 47 evaluable patients receiving imatinib (600 mg/d), the disease control rate was 40.4%, and the median progression-free survival for all patients was 17 wk (95% CI: 3.9-30.1). The median overall survival after dose escalation was 81 wk (95% CI: 36.2-125.8). Adverse events, mainly edema, fatigue, granulocytopenia and skin rash were tolerable. However, further dose escalation (800 mg/d) in 14 cases was ineffective, with disease progression and severe adverse events. Among 30 cases examined for gene mutations, patients with exon 9 mutations experienced a better progression-free survival of 47 wk.

Conclusion: Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

Keywords: Gastrointestinal stromal tumor; Gene mutation; Imatinib; Increased dose.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Asian People
  • Benzamides
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Mutation
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • 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