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Combined Thalidomide and Temozolomide Treatment in Patients with
Glioblastoma Multiforme
Fabian Baumann, Miroslava Bjeljac, Spyros S. Kollias, Brigitta G. Baumert,
Sebastian Brandner, Valentin Rousson, Yasuhiro Yonekawa, René L. Bernays
Department of Neurosurgery
(F.B.,M.B.,Y.Y.,R.L.B.), Institute of Neuroradiology (S.S.K.), Department of Radiation
Oncology (B.G.B.), Department of Neuropathology (S.B.), Department of
Biostatistics (V.R.), University Hospital Zurich, Zurich,
Switzerland
Objectives. Glioblastoma multiforme (GBM) may potentially be
responsive to antiangiogenic therapies as these tumors are highly vascularized
and overexpress angiogenic factors.
Thalidomide exhibits antiangiogenic activity
and may provide additive or synergistic antitumor effects when given
concurrently with temozolomide, an alkylating agent.
To further evaluate this
new concept of combining an antiangiogenic with an alkylating agent, efficacy
and tolerability of thalidomide alone and in combination with temozolomide were
explored in a single-institution, nonrandomized open-label phase II study.
Patients and methods. Forty-four patients with GBMs, who
received thalidomide for a period of at least three months, were evaluated for
survival, time to tumor progression (TTP), and side effects.
Microsurgical tumor
extirpation and radiotherapy preceded chemotherapy.
Nineteen patients (43%)
received thalidomide only (T), and 25 patients (57%) had a combined chemotherapy
of thalidomide and temozolomide (TT).
Median thalidomide dosage was 200 mg/day.
Median temozolomide dosage was 200 mg/m2/day for five days, in
monthly cycles.
Neuroradiological outcomes were assessed by a semiquantitative
grading system.
Results. Median survival was 103 weeks (95% CI, 65–141
weeks) for TT-patients and 63 weeks (95% CI, 49–77 weeks) for T-patients (p
< 0.01).
Median TTP for the TT-group was 36 weeks (95% CI, 20–52 weeks) and
17 weeks (95% CI, 13–21 weeks) for the T-group (p < 0.06).
Neuroradiologically, 14 patients (56%) of the TT-group and six (32%) of the
T-group had evidence of stable disease on at least two successive
neuroradiological follow-ups.
Progressive disease was found in nine patients
(36%) of the TT-group and in 13 (68%) of the T-group.
In two patients (8%) of
the TT-group, a response with tumor regression was found.
Thalidomide and
concurrent temozolomide were safe and well tolerated with mild to moderate
toxicities.
Conclusions. The combination of thalidomide and temozolomide
in the treatment of GBM appears to be more effective than that of thalidomide
alone with respect to survival, TTP, and neuroradiological documentation of
progression, stable disease or response.
Further concurrent prospective studies
of these agents in a larger group of patients with GBM will be required to
establish the soundness of these intriguing observations.
Keywords: antiangiogenic therapy, brain, chemotherapy, glioblastoma
multiforme, survival, temozolomide, thalidomide, treatment
Copyright © 2004 Kluwer Academic Publishers. All rights reserved
Source: doi:10.1023/B:NEON.0000021803.01170.03
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