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Phase II trial of the EGFR
tyrosine kinase inhibitor erlotinib for single agent therapy of recurrent
Glioblastoma Multiforme: Interim results
M. A. Vogelbaum, D. Peereboom, G. Stevens, G. Barnett, C. Brewer
Cleveland Clinic, Cleveland, OH
Background.
Erlotinib (Tarceva, OSI-774) is an orally available small
molecule epidermal growth factor receptor (EGFR) tyrosine kinase
inhibitor.
We have initiated the first phase II trial of erlotinib in single agent therapy
of recurrent glioblastoma multiforme (GBM).
Methods.
Patients with documented recurrent or progressive GBM who have
received previous radiation therapy and cytotoxic chemotherapy were eligible for
enrollment.
No enzyme-inducing anti-epileptic agents were allowed.
Patients were treated with 150 mg of erlotinib per day until tumor progression
or study withdrawal.
Tumor response was determined by MRI.
Analysis for EGFR amplification was performed.
Results.
Interim analysis has been performed on a total of 16 of 31
planned patients as of December, 2003.
Of these, 4 patients have shown partial responses, 1 showed a partial response
of his original tumor but then developed a separate unresponsive focus and 4
have had disease stabilization for greater than 3 months.
Seven patients have had tumor progression within 3 months of starting
erlotinib.
Although a response has been seen in 50% of patients (4 PR + 4 SD), the
responses have not been durable; the median time to progression of responders
has been 145 days after the start of therapy.
Eleven patients have died since the start of the study.
The pattern of subsequent treatment failure in responders has suggested a
diffuse spread of tumor (e.g. gliomatosis cerebri or leptomeningeal
spread).
One patient had a tumor-associated cyst in which the steady state OSI-774 level
was determined and found to be approximately 40% of that observed in
plasma.
Approximately one-half of the tumors have had EGFR amplification, but EGFR
amplification has not ensured a response to erlotinib and responses have been
observed in the absence of amplification.
Conclusions.
Although these results are preliminary in nature, we are
encouraged by the response rate observed to date.
The apparent lack of durability of response and the pattern of post-response
failure may be due, in part, to reduced drug penetration into the brain, an
inadequate dose and/or tumor heterogeneity.
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_19-003423,00.asp
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