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Phase
II Study of Concurrent Continuous Temozolomide (TMZ) and Tamoxifen (TMX) for
Recurrent Malignant Astrocytic Gliomas
Alexander
M. Spence, Richard A. Peterson, Jeffrey D. Scharnhorst, Daniel L. Silbergeld,
Robert C. Rostomily
Department
of Neurology, 356465, University of Washington, Seattle, WA 98195, USA; Tel.:
+1+206-543-2340; Fax: +1-206-685-8100; E-mail: aspence@u.washington.edu
[A.M.S.]. Departments
of Neurology and Neurological Surgery, University of Washington School of
Medicine, Seattle, WA, USA [R.A.P., J.D.S., D.L.S., R.C.R.].
Purpose
and Background.
The
aim of this study was to assess the frequency of response and toxicity in adults
with recurrent anaplastic astrocytoma (AA) or glioblastoma multiforme (GM)
treated with concurrent continuous TMZ and TMX.
Methods.
In
addition to histology, eligibility included age >
18 years, Karnovsky score ≥60,
normal laboratory parameters, no radiotherapy (RT) for 4 weeks, measurable
disease and normal EKG.
The chief exclusions were: previous TMZ, TMX or dacarbazine (DTIC); nitrosourea
within 6 weeks; history of deep venous thrombosis or pulmonary emboli.
All patients (pts) had received prior RT.
TMZ was given at 75 mg/M2/day for 6 weeks, repeated every 10 weeks,
maximum 5 cycles.
Four pts received 60 mg/M2/day for 6 weeks due to extensive prior
chemotherapy exposure.
TMX was started at 40 mg twice daily (b.i.d.) for 1week and then was increased
in three successive weeks to 60, then 80, then 100 mg b.i.d.
Response was assessed before every cycle with MRI ±
gadolinium (Gd).
Results.
Sixteen
pts enrolled: GM 10, AA 6; female 6, male 10; median age 48 (21–58);
prior chemotherapy 7.
There was one partial response and one stable disease.
Eleven pts progressed by the end of cycle 1; three pts failed due to toxicity
before completing cycle 1.
Median time to treatment failure was 10 weeks.
The main toxicities were: transaminitis, pancytopenia, 1st division herpes
zoster, deep vein thrombosis and fatigue.
The study was closed due to the low response rate and frequency of toxicity.
Keywords:
anaplastic
astrocytoma, glioblastoma multiforme, phase II, Tamoxifen, Temozolomide
Copyright
© 2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/123/A/12/abstract.htm
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