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Phase I/II trial of a
twice-daily regimen of temozolomide and celecoxib for treatment of
relapsed/refractory glioblastoma multiforme and anaplastic astrocytoma
S. Pannullo, S. Hariharan, J. Serventi, R. Hayes, C. Balmaceda, J. Burton
JFK Medical Center, Edison, NJ; NYPH-Weill Cornell, New York, NY;
Columbia Presbyterian Hospital, New York, NY; Staten Island University Hospital,
Staten Island, NY
Background.
Combination therapy using agents with different mechanisms of
action and non-overlapping toxicity may be a safe and effective strategy in
cancer therapy.
As seen in Phase I of this trial, BID temozolomide
[Temodar (TMZ)] in combination with celecoxib (Celebrex) is a safe treatment
regimen for malignant glioma.
Phase II of this clinical trial tests the hypothesis that
celecoxib combined with a BID schedule of TMZ is a more effective therapy for
recurrent/progressive malignant glioma.
Methods.
Patients received a loading dose of 200 mg/m2 of TMZ followed by
9 doses of 90 mg/m2 TMZ BID for 5 days of every 28 day cycle.
Celecoxib was given to a maximum dose of 480 mg/m2 for 10
days.
The regimen was well-tolerated by most patients.
Hematologic toxicity was mild and did not recur following
TMZ dose reduction.
Results.
36 patients (22 M, 14 F) received 141 cycles of therapy.
Interim responses were evaluated after 2 cycles.
In the 29 patients evaluable for response, 5/29 (17%) had
a partial response (PR), 21/29 (72.5%) had stable disease (SD), and 3/29 (10.5%)
had progressive disease, resulting in an overall response rate of 90% at 2
months.
One patient had a CR after 7 cycles.
One patient had a PR for 13 cycles but developed spinal
cord tumor.
Average duration of response was 5.2 months (range,
2-13).
The 6-month PFS for 23 evaluable patients was 8/23(35%)
and 6-month overall survival rate of 19/23(83%).
Conclusions.
A regimen of twice-daily TMZ and celecoxib is a safe and
potentially effective regimen for the treatment of recurrent high-grade glioma.
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_19-004202,00.asp
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