Medical Oncology Unit; Department of Experimental and Clinical Medicine; Magna Græcia University and T. Campanella Cancer Center; Catanzaro, Italy.
Department of Biochemistry; Biophysics and General Pathology; Second University of Naples; Naples, Italy.
Cancer Biol Ther. 2014 Jun 1;15(6):707-20. doi: 10.4161/cbt.28557. Epub 2014 Mar 21.
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.
卵巢癌是妇科肿瘤死亡的主要原因。卡铂/紫杉醇是一线治疗的基石。然而，对于复发性/进展性疾病的治疗尚无共识，广泛使用的是多柔比星脂质体（PLD）±卡铂。我们进行了系统评价和荟萃分析，以评估 PLD 为基础的方案与卵巢癌治疗中无 PLD 为基础的方案相比的影响。数据从 2000 年 1 月至 2013 年 1 月期间比较 PLD 为基础的治疗与任何其他方案的随机试验中提取。研究终点是总生存（OS）、无进展生存（PFS）、反应率（RR）、CA125 反应和毒性。提取 OS 和 PFS 的风险比（HRs），并带有 95%置信区间（CI），RR 和 CA125 反应及 3-4 级毒性的比值比（ORs）。使用固定和随机效应模型对选定的终点进行数据汇总。选择了 14 项随机试验，共 5760 例患者，最终进行了分析，结果显示，与其他方案相比，PLD 为基础的方案与 OS 无差异（合并 HR：0.94；95%CI：0.88-1.02；P=0.132），而 PLD 为基础的方案在 PFS 方面有显著获益（HR：0.91；95%CI：0.86-0.96；P=0.001），尤其是在二线（HR：0.85；95%CI：0.75-0.91）和铂敏感（HR：0.83；95%CI：0.74-0.94）亚组中。这项工作证实了该药物独特的耐受性特征，此外，在常见的血液学毒性和 RR、CA125 反应方面，没有观察到差异。与任何其他方案相比，PLD 为基础的方案在疾病的所有阶段均不能改善 OS。仅在铂敏感环境和二线治疗中观察到 PFS 略有优势。
