Phase I/II study of sunitinib malate in Japanese patients with gastrointestinal stromal tumor after failure of prior treatment with imatinib mesylate

Invest New Drugs. 2010 Dec;28(6):866-75. doi: 10.1007/s10637-009-9306-9.


Purpose: To establish a recommended sunitinib dosing schedule in Japanese patients with imatinib-resistant/intolerant gastrointestinal stromal tumor (GIST) and to evaluate the efficacy, safety/tolerability, pharmacokinetics, and pharmacodynamics of sunitinib using this schedule.

Patients and methods: In the phase I part of this open-label phase I/II trial, Japanese GIST patients received 25, 50, or 75 mg/day of sunitinib on Schedule 4/2 (4 weeks on treatment; 2 weeks off treatment) following imatinib failure. In phase II, patients received the recommended (maximum tolerated) dose on this schedule; the primary endpoint was clinical benefit rate (CBR; percent objective responses or stable disease [SD] ≥22 weeks). Additional efficacy, safety, pharmacokinetic, and biomarker analyses were performed.

Results: In phase I (12 patients), the recommended dose was determined to be 50 mg/day. Sunitinib pharmacokinetics were similar to those observed in studies with Western patients. In the phase II part (36 patients), the CBR was 39% (95% CI: 23–57%; 11% partial responses, 28% SD ≥22 weeks). The most common treatment-related non-hematologic adverse events (AEs) were hand–foot syndrome (86%) and fatigue (67%). A trend towards a correlation between decreases from baseline in plasma soluble KIT levels and improved CB was found.

Conclusions: The pharmacokinetics observed and clinical outcomes achieved in Japanese GIST patients on sunitinib (50 mg/day, Schedule 4/2) after imatinib failure appeared similar to those of Western patients in previous sunitinib trials. Although some serious AEs were observed, AEs were generally manageable using dose interruption/modification and/or standard medical treatments.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Asian Continental Ancestry Group*
  • Benzamides
  • Biomarkers, Tumor / blood
  • Demography
  • Female
  • Gastrointestinal Stromal Tumors / blood
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Humans
  • Imatinib Mesylate
  • Indoles / adverse effects
  • Indoles / blood
  • Indoles / pharmacokinetics
  • Indoles / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / blood
  • Pyrroles / pharmacokinetics
  • Pyrroles / therapeutic use*
  • Solubility
  • Sunitinib
  • Treatment Failure
  • Young Adult


  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Indoles
  • Neoplasm Proteins
  • Piperazines
  • Pyrimidines
  • Pyrroles
  • Imatinib Mesylate
  • Sunitinib