Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma

Cancer. 2004 Mar 15;100(6):1199-207. doi: 10.1002/cncr.20073.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use*
  • Drug Carriers
  • Female
  • Glioma / drug therapy*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Quality of Life
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Drug Carriers
  • Peptides
  • doxorubicin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer
  • Tamoxifen
  • Polyethylene Glycols
  • Doxorubicin