I study of STI571 (Gleevec) for patients with recurrent malignant gliomas and
meningiomas (NABTC 99-08)
Y Wen, W K Yung, Kenneth Hess, Sandra Silberman, Michael Hayes, David Schiff,
Frank Lieberman, Timothy F Cloughesy, Lisa M DeAngelis, Susan M Chang, Larry
Junck, Howard A Fine, Karen Fink, H I Robins, Jeffrey J Raizer, Lauren E Abrey,
Minesh P Mehta, Elizabeth A Maher, Peter M Black, John Kuhn, Renaud Capdeville,
Richard S Kaplan, Anthony Murgo, Charles Stiles, Michael D Prados
Cancer Inst, Boston, MA; M.D. Anderson Cancer Center, Houston, TX; Novartis
Oncology, E. Hanover, NJ; University of Pittsburgh Medical Center, Pittsburgh,
PA; Uinversity of California Los Angeles, Los Angeles, CA; Memorial
Sloan-Kettering Cancer Center, New York, NY; Univ of California San Francisco,
San Francisco, CA; University of Michigan, Ann Arbor, MI; National Institutes of
Health, Washington, DC; University of Texas, Southwestern Medical Center,
Dallas, TX; University of Wisconsin, Madison, WI; Brigham and Women's Hospital,
Boston, MA; University of Texas, San Antonio, TX; Novartis Oncology, Basle,
Switzerland; National Cancer Institute, Washington, DC.
(Gleevec) is a small molecule tyrosine kinase inhibitor of the BCR-ABL and c-kit
tyrosine kinases, as well as the receptors for platelet-derived growth factor
PDGF and its receptors are frequently expressed together in gliomas raising the
possibility that an autocrine/paracrine loop may contribute to the pathogenesis
of these tumors.
PDGF may also play an important role in the angiogenesis associated with
In preclinical studies, STI571 inhibited the growth of U343 and U87 glioblastoma
cell lines in vitro and in orthotopic murine models with subcutaneous and
intracranial tumors (Cancer Res 2000;60:5143-5150).
These studies suggest that STI571 may have therapeutic potential in patients
with malignant gliomas.
The North American Brain Tumor Consortium (NABTC) began a phase I/II study of
STI571 in patients with recurrent malignant gliomas and meningiomas in March,
2001 (NABTC 99-08).
Patients were assigned to one of two groups depending on whether they are taking
enzyme inducing anti-epileptic drugs or not.
To date, 40 patients have been enrolled.
Cohorts of patients were treated with 400, 600, 800, and most recently 1000
mg/day of STI571.
Histologies include 24 GBM, 8 anaplastic oligodendroglioma, 6 anaplastic
astrocytoma, 1 anaplastic mixed glioma and 1 meningioma.
MTD has not yet been determined.
Two patients experienced grade 5 toxicity (1 intracerebral hemorrhage in the
setting of tumor progression and thrombocytopenia; 1 pneumocystis pneumonia in a
patient on corticosteroids), 4 patients had grade 4 toxicity and 10 had grade 3
Of the 31 patients to date who were evaluable for response, 14 patients had
stable disease, 4 longer than 24 weeks.
The final results of the phase I study and pharamcokinetic data will be
Copyright 2002 American Society of Clinical Oncology