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Pegylated liposomal doxorubicin in the management of ovarian cancer: a systematic review and metaanalysis of randomized trials.

Abstract
Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no consensus for management of recurrent/progressive disease, in which pegylated liposomal doxorubicin (PLD) ± carboplatin is widely used. We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment. Data were extracted from randomized trials comparing PLD-based treatment to any other regimens in the January 2000-January 2013 time-frame. Study end-points were overall survival (OS), progression free survival (PFS), response rate (RR), CA125 response, and toxicity. Hazard ratios (HRs) of OS and PFS, with 95% CI, odds ratios (ORs) of RR and risk ratios of CA125 response and grade 3-4 toxicity, were extracted. Data were pooled using fixed and random effect models for selected endpoints. Fourteen randomized trials for a total of 5760 patients were selected and included for the final analysis, which showed no OS differences for PLD-based compared with other regimens (pooled HR: 0.94; 95% CI: 0.88-1.02; P = 0.132) and a significant PFS benefit of PLD-based schedule (HR: 0.91; 95% CI: 0.86-0.96; P = 0.001), particularly in second-line (HR: 0.85; 95% CI: 0.75-0.91) and in platinum-sensitive (HR: 0.83; 95% CI: 0.74-0.94) subgroups. This work confirmed the peculiar tolerability profile of this drug, moreover no difference was observed for common hematological toxicities and for RR, CA125 response. PLD-containing regimens do not improve OS when compared with any other schedule in all phases of disease. A marginal PFS advantage is observed only in platinum-sensitive setting and second-line treatment.
AuthorsNicoletta Staropoli, Domenico Ciliberto, Cirino Botta, Lucia Fiorillo, Anna Grimaldi, Stefania Lama, Michele Caraglia, Angela Salvino, Pierfrancesco Tassone, Pierosandro Tagliaferri
JournalCancer biology & therapy (Cancer Biol Ther) Vol. 15 Issue 6 Pg. 707-20 (Jun 01 2014) ISSN: 1555-8576 [Electronic] United States
PMID24658024 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)
Chemical References
  • Antibiotics, Antineoplastic
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
Topics
  • Antibiotics, Antineoplastic (adverse effects, therapeutic use)
  • Disease-Free Survival
  • Doxorubicin (adverse effects, analogs & derivatives, therapeutic use)
  • Female
  • Humans
  • Ovarian Neoplasms (drug therapy, mortality)
  • Polyethylene Glycols (adverse effects, therapeutic use)
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

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