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Pegylated liposomal doxorubicin-efficacy in
patients with recurrent high-grade glioma
Hau P, Fabel K, Baumgart U, Rummele P, Grauer O, Bock A, Dietmaier C,
Dietmaier W, Dietrich J, Dudel C, Hubner F, Jauch T, Drechsel E, Kleiter I,
Wismeth C, Zellner A, Brawanski A, Steinbrecher A, Marienhagen J, Bogdahn U
Klinik und Poliklinik fur Neurologie der Universitat Regensburg,
Regensburg, Germany. peter.hau@medbo.de
Background. Doxorubicin exhibits high efficacy in malignant glioma
cell cultures.
Nonetheless, as a standard formulation, doxorubicin has not been used
clinically, due to poor penetration of the blood-brain barrier.
Furthermore, doxorubicin is known to induce tumor resistance genes.
To address both of these issues, the authors investigated the use of pegylated
liposomal doxorubicin (Caelyx; Essex Pharma, Munich, Germany) alone (Trial 1)
and in combination with tamoxifen (Trial 2) in two sequentially performed
nonrandomized prospective Phase II trials involving patients with recurrent
high-grade glioma.
Methods. Twenty patients were included in each trial.
Progression-free survival at 6 months (PFS-6) and toxicity were the primary
endpoints.
Expression of the tumor resistance proteins multidrug resistance protein 1
(MDR-1) and multiple resistance protein (MRP) was evaluated by
immunohistochemical methods and by sestamibi-single-photon emission computed
tomography (SPECT).
Results. The overall response rate (including cases of disease
stabilization) was 40% in both Trial 1 and Trial 2.
PFS-6 was 15%, and the median time to disease progression was 17 weeks.
It is noteworthy that 40% of patients with Grade III tumors had long-term
responses, which lasted for up to 3 years.
There was no significant difference between Trial 1 and Trial 2 in terms of
efficacy.
Both regimens were well tolerated, with the main side effect being palmoplantar
erythrodysesthesia.
The authors found no correlation between clinical response and expression of
tumor resistance genes or between clinical response and SPECT data.
Conclusions. Pegylated liposomal doxorubicin administered alone or in
combination with tamoxifen is safe and moderately effective in patients with
recurrent high-grade glioma.
None of the putative predictors for response that were evaluated proved to be
significant in this setting.
Copyright 2004 American Cancer Society.
PMID: 15022287 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15022287
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