title: 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.
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Staropoli
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ciliberto
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Fiorillo
authors.affiliation: Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lama
authors.affiliation: Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Salvino
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: metaanalysis; ovarian cancer; pegylated liposomal doxorubicin; randomized clinical trials; systemic chemotherapy