Phase II Study Of STI571 (GleevecTM) For Patients With Small Cell Lung Cancer

Reviewer: Roberto Santiago, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2002

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Presenter: Bruce E Johnson
Presenter's Affiliation: Dana-Farber Cancer Inst, Boston, MA
Type of Session: Scientific

Background

  • STI571 is a small molecule that inhibits the tyrosine kinase activity of the BCR-Abl and Kit receptors
  • The oral preparation of STI571 has been proven safe and very efficacious against CML (BCR-ABL positive) and GIST (Kit positive)
  • The activation of the Kit receptor by the ligand ?stem cell factor? (SCF) has been implicated in the establishment of an autocrine growth loop in small cell lung cancer (SCLC)
  • Published literature has suggested that Kit is expressed on 50-70% of SCLC cells

Materials and Methods

  • Phase II trial designed to evaluate STI571 in patients with SCLC who were either chemotherapy naïve (CN) or had maintained a response for ≥ 60 days to a previous treatment (sensitive relapse, SR)
  • Enrollment of CN patients was limited to patients with extensive stage SCLC
  • The primary end point was objective response rate (OR) to STI571 (600 mg/day)
  • Between 11/006 and 4/01, 16 men and 3 women with histologically-confirmed SCLC were enrolled on the trial; 9 were CN with extensive stage SCLC and 10 were in SR
  • ECOG performance status ranged from 0-2 (0, 42%; 1, 47%; and 2, 11%)
  • The median age was 58 (range 39-74)

Results

  • No grade 4 tocixity was observed
  • One case of grade 3 vomiting and one case of grade 3 CNS toxicity (seizure) were observed
  • No OR were observed
  • The median time to tumor progression was 24 days (range 18-52 days) in the CN patients
  • The median time to tumor progression was 42 days (range 7-126 days) in the SR patients
  • One patient had stable disease for 90 days
  • Immunohistochemical staining for Kit was performed in 14 tumor blocks
  • Only 28% (4/14) stained positive for Kit
  • The time to tumor progression for the 2 CN patients with tumors positive for Kit were 37 and 52 days
  • The time to tumor progression for the 2 SR patients with tumors positive for Kit were 35 and 68 days
  • The 6-months overall survival was 68%

Author's Conclusions

  • STI571 was well tolerated in SCLC patients
  • The study is limited by the small number of patients, particularly Kit positive patients
  • Immunohistochemical tests for Kit yielded a lower rate of Kit positivity than that described on the literature for SCLC cells
  • The objective response to STI571 in these SCLC patients was disappointedly low

Clinical/Scientific Implications

  • Any conclusions from this study should take into account the small number of Kit positive SCLC patients actually treated
  • Some of the studies suggesting higher rates of Kit expression on SCLC cells have used other techniques for detection such as FISH
  • Further testing of STI571 as a single agent will focus on confirmation of SCLC histology and the demonstration of Kit expression

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.


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