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A phase II trial
of erlotinib (OSI-774) in patients (pts) with recurrent malignant gliomas (MG)
not on EIAEDs
J. J. Raizer, L. E. Abrey, P. Wen, T. Cloughesy, I. A. Robins, H. A. Fine, F.
Lieberman, V. K. Puduvalli, K. L. Fink, M. Prados
Northwestern University, Feinberg
School of Medicine, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New
York, NY; Dana-Farber Cancer Institute, Boston, MA; University of California,
Los Angeles, Los Angeles, CA; University of Wisconsin Hospital & Clinics,
Madison, WI; Neuro-Oncology Branch, NCI, NIH, Bethesda, MD; University of
Pittsburgh, Pittsburgh, PA; U Texas M. D. Anderson Cancer Center, Houston, TX; U
Texas Southwestern Medical Center, Dallas, TX; University of California, San
Francisco, CA.
Purpose. To evaluate the efficacy of
OSI-774, a small molecule tyrosine kinase inhibitor of the epidermal growth
factor receptor (EGFR), in patients with recurrent malignant gliomas not on
enzyme induce anti-convulsant drugs (EIAEDs).
Methods.
Pts with recurrent MG were treated with OSI-774 at a dose of 150 mg/day
continuously.
Patients could not have had more than 2 prior chemotherapies.
Patients were evaluated for response with MRI every 56 days.
PK studies and AGP levels were done in most patients.
Results.
67 pts enrolled onto this arm of the study but only the 45 pts with recurrent MG
are reported here.
Histology.
30 (20M/10F) pts had glioblastoma multiformes (GBMs) and 15 (7M/8F) pts had
anaplastic gliomas (AGs).
Median age and KPS was 58 years and 80 for GBMs and 43 years and 90 for
AGs.
The median PFS for GBM was 12 wks (95% CI; 7.6 to 13 weeks) with no GBM pts
progression free at 24 weeks; best response was SD in 4 pts.
For AGs median PFS was 8.6 wks (CI; 3.7 to 45 wks) with 4 patients still on
study; best response was 1 PR (unconfirmed) and 2 SD.
Cycle 1 toxicities: Gr 3-Rash and hypokalemia all others were Gr 1 and 2,
primarily rash, diarrhea, fatigue, and bilirubin elevation.
PK studies on 20 pts, found an AUC0-24 for OSI-774 was 13.1 ugxh/ml
and for OSI-420 875 ngxh/ml; the Cpmax (ng/ml) was 895 and 64 for OSI-774 and
OSI-420.
Conclusion.
We completed a phase II trial of OSI-774 in patients with MGs not on
EIAEDs.
While a few patients had SD and 1 had a PR the median PFS and the 24 week PFS
suggest that for GBMs and AGs that OSI-774 has limited activity as a single
agent.
Toxicities were primarily Gr 1 and 2 and tolerable.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00858,00.asp
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