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Meta-Analysis
. 2014 Jun 1;15(6):707-20.
doi: 10.4161/cbt.28557. Epub 2014 Mar 21.

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

Nicoletta Staropoli  1 , Domenico Ciliberto  1 , Cirino Botta  1 , Lucia Fiorillo  1 , Anna Grimaldi  2 , Stefania Lama  2 , Michele Caraglia  2 , Angela Salvino  1 , Pierfrancesco Tassone  1 , Pierosandro Tagliaferri  1
Affiliations
Meta-Analysis

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

Nicoletta Staropoli et al. Cancer Biol Ther. .

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.

Keywords: metaanalysis; ovarian cancer; pegylated liposomal doxorubicin; randomized clinical trials; systemic chemotherapy.

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Figures

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Figure 1. PRISMA chart showing the trial exclusion and inclusion process in the metaanalysis. SEER, Surveillance, Epidemiology, and End Results.
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Figure 2. Comparison of OS and PFS, according to treatment line (A andB respectively) or platinum sensitivity (C and D respectively), between patients treated with a PLD-containing regimen vs. any other PLD-free schedule. Abbreviation: OS, overall survival; PFS, progression free survival; HR, hazard ratio; CPLD, carboplatin and pegylated liposomal doxorubicin; CP, carboplatin and paclitaxel; PLD pegylated liposomal doxorubicin; O, olaparib; C, carboplatin; G, gemcitabine; T, topotecan.
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Figure 3. Comparison of RR and Ca125 response, according to treatment line (A and B respectively) or platinum sensitivity (C andD respectively), between patients treated with a PLD-containing regimen vs. any other PLD-free schedule. Abbreviation: OR, odds ratio; rr, risk ratio; CPLD, carboplatin and pegylated liposomal doxorubicin; CP, carboplatin and paclitaxel; PLD, pegylated liposomal doxorubicin; O, olaparib; C, carboplatin; G, gemcitabine; T, topotecan.
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Figure 4. Funnel plot (Begg test) assessing publication bias.
See this image and copyright information in PMC

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