Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg

Eur J Cancer. 2005 Aug;41(12):1751-7. doi: 10.1016/j.ejca.2005.04.034.


In the EORTC-ISG-AGITG trial 946 patients with advanced gastro-intestinal stromal tumours (GIST) were randomised to receive 400 or 800 mg of imatinib daily. An increase in progression free survival (PFS) was demonstrated for patients randomised to the high-dose arm. Patients randomised to low-dose could cross-over to high-dose upon progression. We evaluated the feasibility, safety and efficacy of this policy. Of the 241 patients available for follow-up, 133 patients (55%) crossed over to high-dose imatinib according to the protocol. Of these patients, 92% had not had a prior dose reduction. The cumulative incidence of subsequent dose reductions after cross-over was 17% after six months with 51% discontinuing therapy without requiring a dose reduction. The extent of anaemia and fatigue increased significantly after cross-over, whilst neutropenia was less severe than during low-dose treatment. Objective responses after cross-over included three patients (2%) with a partial response and 36 (27%) with stable disease. The median PFS after cross-over was 81 days, although 18.1% of patients were still alive and progression free one year after cross-over. We conclude that a cross-over to high-dose imatinib is feasible and safe in GIST patients who progress on low-dose therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Benzamides
  • Cross-Over Studies
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Feasibility Studies
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Treatment Outcome


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate