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.