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Adjuvant chemotherapy
with temozolomide and pegylated liposomal doxorubicin in the first-line therapy
of patients with glioblastoma – a phase-II trial
P. Hau, T. Jauch, B. Hirschmann, E. Drechsel, O. Grauer, H. Koch, C. Wismeth,
A. Steinbrecher, U. Bogdahn
University of Regensburg, Regensburg, Germany
Background. Temozolomide (Temodar) recently
showed promising results in the first-line therapy of glioblastoma (Stupp R,
2002).
Pegylated liposomal doxorubicin PLD (Caelyx/Doxil) was successfully evaluated in
patients with recurrent high-grade glioma (Fabel K, 2001; Hau P, 2002).
Therefore, a combination of both agents seems promising.
Here, we update data on a pilot phase II-trial using this regimen.
Methods. We
initiated a combination regimen consisting of temozolomide (TMZ) and PLD in the
first-line therapy of patients with glioblastoma.
TMZ is given during standard radiotherapy (initiation) and on days 1-5 in 28
days starting 4 weeks after completion of radiotherapy (maintainance).
PLD is given as a short-time infusion in a dose-escalation regimen once prior to
radiotherapy (initiation) and on days 1 and 15 starting 4 weeks after completion
of radiotherapy (maintainance).
PLD is escalated for 5mg/m2 in groups of three patients with a highest dose of
20mg/m2 (group 4).
Primary end point is tumor progression.
Results. In
the first treatment group using the standard dose of TMZ and 5mg/m2 of PLD, only
one out of 7 evaluable patients had a dose limiting toxicity (DLT).
In the second treatment group using 10mg/m2 of PLD, the regimen was tolerated
without DLT.
Concerning efficacy in the ″treated-patients″ analysis of 11
patients treated so far, 1 had a partial response in MRI and 8 patients had
tumor stabilization 4 weeks after conclusion of radiotherapy.
As no DLT was observed in dose group 2, the regimen was escalated recently to
treatment group 3 (15mg/m2 PLD).
Discussion.
Considering
preliminary results, this regimen is feasible, tolerable, and able to induce
objective responses in patients with glioblastoma using the standard dose of TMZ
and 5 or 10mg/m2 of PLD.
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_19-00331,00.asp
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