Efficacy and Cardiotoxicity of Liposomal Doxorubicin-Based Chemotherapy in Advanced Breast Cancer: A Meta-Analysis of Ten Randomized Controlled Trials

PLoS One. 2015 Jul 23;10(7):e0133569. doi: 10.1371/journal.pone.0133569. eCollection 2015.

Abstract

Background: Various trials have compared the efficacy and toxicity of liposomal doxorubicin-based chemotherapy with the conventional formulation of doxorubicin although arriving at inconsistent conclusions. To derive a conclusive assessment of the efficacy and cardiotoxicity associated with chemotherapy, we performed a meta-analysis by combining data from all eligible randomized controlled trials.

Methods: We used the PubMed database to identify relevant studies published through December 28, 2014. Eligible studies included randomized controlled trials directly comparing the efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy with conventional doxorubicin in advanced breast cancer with adequate data. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the efficacy and cardiotoxicity in a fixed-effects or random-effects model.

Results: Ten randomized controlled trials containing efficacy and data from a total of 2,889 advanced breast cancer patients were included in this report. Liposomal doxorubicin-based chemotherapy was associated with a significant reduction in the risk of cardiotoxicity (OR = 0.46, 95% CI 0.23 to 0.92, p = 0.03) and a significant improvement in the overall response rate (ORR) (OR = 1.25, 95% CI 1.02 to 1.52, p=0.03) compared with conventional doxorubicin. An apparent improvement in progression-free survival (PFS) for patients treated with liposomal doxorubicin-based chemotherapy was noted; however, this difference was not significant (HR = 1.14, 95% CI 0.96 to 1.34, p = 0.12). In terms of overall survival (OS), no significant difference between the two chemotherapy regimens was noted (HR = 1.00, 95% CI 0.91 to 1.10, p = 0.93).

Conclusion: The results of this meta-analysis suggest that liposomal doxorubicin-based chemotherapy is associated with a significant improvement in the ORR and a significant reduction in the risk of cardiotoxicity.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Combined Modality Therapy
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives
  • Female
  • Heart Diseases / chemically induced
  • Humans
  • Liposomes / administration & dosage
  • Multicenter Studies as Topic
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Randomized Controlled Trials as Topic*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Liposomes
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin

Grants and funding

The authors received no specific funding for this work.