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Liposomal
doxorubicin with and without tamoxifen in the salvage treatment of high grade
glioma - a phase-II study
Peter
Hau, Joerg Dietrich, Klaus Fabel, Ulrike Baumgart, Oliver Grauer, Tanya Jauch,
Anton Zellner, Martin Proescholdt, Andreas Steinbrecher, Alexander Brawanski,
Peter Krauseneck, Ulrich Bogdahn
University
of Regensburg, Regensburg, Germany; Nervenklinik Bamberg, Bamberg, Germany
Purpose.
Resistance to chemotherapeutic agents and poor blood brain barrier (BBB)
penetration are major obstacles in the treatment of malignant glioma.
Doxorubicin is known to be effective in high-grade glioma cell lines and was
shown to cross BBB in a liposomal encapsulated formulation (Caelyx®, CAE).
In two subsequent phase II-studies, CAE was administered as a single agent or in
combination with Tamoxifen (TAM) in patients with recurrent malignant glioma.
Methods.
Applying an intention-to-treat design, 40 patients with recurrent high-grade
glioma (grade IV, n = 28; grade III, n = 12) were included and treated with
intravenous CAE 20 mg/sqm BS every two weeks (20 patients) and, in the second
study, with CAE plus oral TAM in a continuous daily dose of 480 mg (20
patients).
Every 6 weeks, response was evaluated clinically and by use of MRI.
Results.
The single agent regimen and the combination therapy were equally well
tolerated, with major side effects being palmaroplantar erythrodysesthesia in
17/40 patients and myelosuppression (WHO grade III) in 10/40 patients.
Cardiac toxicity has not been observed so far.
TAM was well tolerated even in this high doses with deep venous thrombosis in a
single patient. In both regimens together, 16/40 (40%) patients showed objective
responses with partial response in 2/40 and disease stabilization in 14/40
patients.
Response rates in the CAE regimen (45%) vs. the CAE/TAM regimen (35%) were
significantly different, but in the latter regimen, 16 patients had grade IV
tumors in comparison to 11 in the CAE regimen.
Median overall survival after initiation of salvage therapy was 32 weeks for CAE
and 24 weeks for CAE/TAM, or 28 weeks for grade-IV and 24 weeks for grade-III,
respectively.
Discussion.
Single agent therapy with CAE and the combination of CAE and TAM appear to have
similar moderate activity in heavily pretreated patients with recurrent
high-grade glioma.
Both regimens are save concerning myelotoxicity, skin toxicity and cardiac
complications.
© Copyright 2002 American
Society of Clinical Oncology
Source:
http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-00312-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
&returnpid=2323
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