STI 571, An Active Drug In Metastatic Gastro Intestinal Stromal Tumors (GIST), An EORTC Phase I Study

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: Allan T. Van Oosterom
Affiliation: EORTC Soft Tissue and Bone Sarcoma Group, Brussels, Belgium


    The overall survival for patients with GISTs is poor with an estimated 10 to 20 month median survival in patients with metastatic disease. GISTs are characterized by expression of the c- kit proto-oncogene product (KIT) in 100% of cases and unresponsiveness to any type of systemic/local treatment. STI-571 is an orally available, small molecule inhibitor of Abl, KIT and PDGFR. Daily administration of STI-571 has already shown activity in CML. Data on the STI- 571 effect in solid tumors are lacking. It also is conceivable that solid tumor patients tolerate the drug differently from leukemia patients. For these reasons the EORTC decided to perform a phase I study in patients with GIST and other soft tissue sarcoma (STS) subtypes to determine the maximum tolerated dose (MTD) of STI-571.

Materials and Methods:

  • Between August 3, 2000 and November 1, 2000, 20 patients were entered in the study.
  • The median age was 50 years (range 29-68), male/female ratio was 13/7, the WHO-PS median was 1 (range 0-2).
  • Dose levels started at 400 mg po once daily and then were increased to 600 mg/d and 800 mg/d in twice daily dosing.
  • 16 patients had received prior chemotherapy
  • End point of the study was maximum tolerated dose.


  • Eight patients received 400 mg of STI-571 once daily, 8 received 300 mg bid and 4 received 400 mg bid
  • 11% of patients were discontinued with progressive disease, 3 of them had non-GIST histology.
  • Of the remaining 15 patients, 36% had formal radiological partial response on assessment, 33% had unofficial PR (that is a 20 to 29% reduction in tumor size) and symptomatic improvement, 3 are too early to evaluate.
  • Dramatic reduction in 18FDG uptake at PET scanning on day 8 was observed in 14 patients with 8 CR and 4 PR at day number 8.
  • Toxicity was mainly mild to moderate, and included nausea, upper abdominal discomfort, diarrhea, liver function test abnormalities, rash and peri-orbital edema.
  • At 300 mg bid reversible grade 3 rash was noted in 1 patient and at 400 mg bid grade 4 neutropenia with fever, qualifying for dose limiting toxicity, have been observed.
  • In addition, in 3 cases tumor bleeding has been reported possibly because of rapid tumor lysis. One patient discontinued drug for non-drug related reason, and was not evaluated.

Authors' Conclusions

  • STI-571 was fairly well tolerated.
  • The MTD in STS patients may be 400 mg bid or above.
  • Impressive clinical activity was observed in GIST.

Clinical/Scientific Implications:

    This study demonstrates that STI-571 is a very active targeted agent against Gastrointestinal stromal tumors. The FDA has approved this drug for use in CML. STI-571 is well touted in the lay press as a wonder drug without side effects. This study, while clearly demonstrating this drug's activity, also demonstrates that STI571 is not without toxicity. Thus, patients using this drug must be monitored closely. This study shows the continued importance of evaluating molecularly targeted therapies.

OncoLink ASCO 2001 coverage is provided by an unrestricted educational grant from Amgen