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Pegylated liposomal doxorubicin in the management of ovarian cancer: A systematic review and metaanalysis of randomized trials
Authors:Nicoletta Staropoli  Domenico Ciliberto  Cirino Botta  Lucia Fiorillo  Anna Grimaldi  Stefania Lama  Michele Caraglia  Angela Salvino  Pierfrancesco Tassone  Pierosandro Tagliaferri
Affiliation:1.Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy;2.Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy
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:ovarian cancer   systemic chemotherapy   pegylated liposomal doxorubicin   randomized clinical trials   metaanalysis
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