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Journal of Neuro-Oncology
70 (1): 91-95, October 2004
Copyright © 2004 Kluwer Academic Publishers
All rights reserved
Alexander M. Spence
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
Richard A. Peterson
Departments of Neurology and Neurological Surgery, University of
Washington School of Medicine, Seattle, WA, USA
Jeffrey D. Scharnhorst
Departments of Neurology and Neurological Surgery, University of
Washington School of Medicine, Seattle, WA, USA
Daniel L. Silbergeld
Departments of Neurology and Neurological Surgery, University of
Washington School of Medicine, Seattle, WA, USA
Robert C. Rostomily
Departments of Neurology and Neurological Surgery, University of
Washington School of Medicine, Seattle, WA, USA
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 (2158); 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
Article ID: 5379147