复发上皮性卵巢癌化疗疗效的Meta分析

摘要

目的：系统评价不同化疗方案治疗复发上皮性卵巢癌（EOC）的临床疗效差异及毒副反应等。方法：按Cochrane系统评价方法，计算机检索PubMed、Embase、Medline、Cochrane Library、循证医学数据库（EBMR）、中国生物医学文献数据库（CBM）、中国期刊全文数据库（CJFD）、中国知网（CNKI）等数据库，并手工检索相关领域杂志。检索期限自1995年1月1日-2011年12月31日。查找复发性EOC治疗中评价了两种化疗方案对患者无进展生存期（PFS）、整体生存时间（OS）、缓解人数、完全缓解人数、3~4度血液学毒性反应、非血液学毒性反应等的随机对照试验（RCT），由2位研究者按照纳入排除标准筛选文献、评价质量并提取资料后，采用RevMan5.1软件进行Meta分析。结果：共纳入14个研究（7个评价治疗敏感型复发EOC，7个评价治疗耐药型复发EOC）。Meta分析结果显示，卡铂联合化疗较单一卡铂可以改善敏感型复发EOC患者的OS（OR=0.50，95%CI：0.32~0.78，P=0.002）及缓解率（OR=1.87，95%CI：1.38~2.55，P＜0.0001），但无助于改善PFS（OR=1.19，95%CI：0.60~2.33，P=0.62），会增加3~4度白细胞降低的风险（OR=7.82，95%CI：4.00~15.30，P＜0.00001）。两项研究提示拓扑替康可以改善耐药型复发EOC的OS，吉西他滨与脂质体阿霉素相比并不增加改善耐药型复发EOC的缓解率（OR=1.29，95%CI：0.67~2.46，P=0.45），但增加3~4度中性粒细胞降低的风险（OR=2.97，95%CI：1.70~5.17，P=0.0001）。结论：卡铂联合化疗可以改善敏感型复发EOC患者的OS及缓解率，化疗过程中要注意监测血液学毒性反应。拓扑替康可以改善耐药型复发EOC的OS但无助于改善PFS，可以作为今后治疗耐药型复发EOC的研究方向。尚需更多设计严格的高质量RCT研究加以证实。%Objective:To systematically assess the clinical efficacy and toxic reaction of different chemotherapy regimens for recurrent epithelial ovarian cancer. Methods:The literature spublished between January 1,1995 and December 31,2011 in PubMed,Embase,Medline,Cochrane Library,EBMR,CBM,CJFD,and CNKI were searched. The RCT were searched which about the effect of different chemotherapy regimens on the progress free survival (PFS),overall survival (OS),the number of responses,complete responses,grade 3-4 hematologic toxicity reaction,grade 3-4 nonhematologic toxicity reaction for recurrent epithelial ovarian cancer. The literatures were screened according to the inclusive and exclusive criteria by two reviewers independently,then the RevMan 5.1 software was used for meta-analyses. Results:14 RCT (including 7 for platinum-sensitive and 7 for platinum-resistance) were included. Meta analysis showed that carboplatin-based chemotherapy was a favorable factor for OS (OR=0.50,95%CI:0.32-0.78,P=0.002) and responses rate (OR=1.87,95%CI:1.38-2.55,P<0.000 1) in platinum-sensitive patients,but it was not a favorable factor for PFS (OR=1.19,95%CI:0.60-2.33,P=0.62)and can increase the risk of leukocyte reduction. Two studies show that topotecan can improve OS in platinum-resistance patients. Gemcitabine was not a favorable factor for responses rate (OR=1.29,95%CI:0.67-2.46,P=0.45) and can increase the risk of neutropenia reduction (OR=2.97,95%CI:1.70-5.17,P=0.000 1) compared with PLD in platinum-resistance patients. Conclusions:Carboplatin-based chemotherapy can be improve OS and responses rate in platinum-sensitive patients ,It should pay attention to monitor hematologic toxicity reaction during chemotherapies. Topotecan can improve OS but it was not a favorable factor for PFS in platinum-resistance patients. It can be used as research direction in the future for platinum-resistance patients. It is not a high methodological quality studies in this meta analysis and still need more rigorous quality RCT study to confirmed.