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Erlotinib HCL for
glioblastoma multiforme in first relapse, a phase II trial
A. Yung, J. Vredenburgh, T. Cloughesy, B. J. Klencke, P. S. Mischel, D. D.
Bigner, K. Aldape, S. Vanderburg, M. Prados, The Accelerate Brain Cancer Cure
Group
MD Anderson Cancer Center, Houston, TX; Duke University,
Raleigh-Durham, NC; University of California Los Angeles, Los Angeles, CA;
Genentech Inc., South San Francisco, CA; University of California San Francisco,
San Francisco, CA.
Background.
Erlotinib HCL (Tarceva), an orally active, highly potent and
selective inhibitor of the epidermal growth factor receptor (HER1/EGFR), has
documented clinical activity in glioblastoma multiforme (GBM) (M Prados ASCO
02).
GBM is an interesting target for EGFR inhibitors because of the high rate of
EGFR gene amplification and activating mutations in EGFR (i.e. EGFRvIII).
Methods.
A multi-institutional phase II clinical trial of the single
agent Tarceva was initiated in August 2003 for GBM patients with measurable
disease in first relapse.
Tarceva is metabolized by CYP3A4, therefore to ensure adequate exposure patients
receiving enzyme-inducing anti-epileptic drugs (EIAED group) receive a higher
starting dose (300mg/d), otherwise standard dose of 150mg/d was given (non-EIAED
group).
Individual dose titration until dose-limiting toxicity (diarrhea, rash, other)
was allowed, from 150 to 200mg (non-EIAED group) or from 300 to 500mg in 50-mg
increments (EIAED group).
Results.
Forty-eight subjects (19 female, 29 male) with a median age of
50 years (37-70) have been enrolled to date.
21 on concurrent EIAEDs; 27 received 150mg/d initially.
23 of the 48 subjects have been able to dose escalate at least once, 2 are now
receiving 450 or 500mg, and 1 discontinued therapy on day 10 due to skin
toxicity at their 300mg/d starting dose.
Pharmacokinetic measurements are being obtained in this study.
At week 8, 1 subject had a CR, 1 subject achieved PR (unconfirmed), 11 had
stable disease (SD) although 4 of the SD subjects have subsequently
progressed.
To date, 27 patients have progressed and 1 is not evaluable.
Gene amplification, as determined by FISH, has been seen in 16 of 30
subjects.
Conclusions.
These preliminary data suggest that erlotinib is active in
recurrent GBM.
Updated results, including the association between EGFR status, including gene
amplification status, IHC expression, and EGFRvIII status, will be presented.
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_19-003313,00.asp
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