托泊替康治疗复发性卵巢癌的系统评价

目的评价托泊替康在复发性卵巢癌化疗中的疗效,安全性以及成本效果。方法计算机检索MEDLINE(1966～2005),EMbase(1974～2005), CancerLit(1996～2003),中国生物医学文献数据库(1978-2005)。中国期刊全文数据库(1 994～2005),The Cochrane Central Register of Controlled Trials(CENTRAL),The National Research Register,Health Technology Assessment Database(HTA),Cochrane图书馆(2005年第3期)等数据库。手工检索相关领域的杂志,并用Google等搜索引擎在互联网上查找相关的文献。检索截止至2005年12月。收集有关托泊替康(TPT)与其他药物比较治疗复发性卵巢癌(ROC)的随机对照试验(RcT)文献。由两名研究者独立评价纳入研究的文献质量,并提取有效数据进行Meta分析。结果共纳入4个RCT(9篇文献,1 032例病人)。其中1个多中心RCT(474例,B级),比较TPT与脂质体阿霉素(PLD)治疗ROC的疗效和成本;另1个多中心RCT(226例,A级),比较托泊替康与紫杉醇的疗效。还有1个RCT (266例,B级)为TPT不同用药途径的比较;最后1个RCT(66例,A级)比较了TPT两种用药方案及剂量。结果显示:①TPT与紫杉醇比较:临床受益率TPT大于紫杉醇,两者差异有统计学意义;缓解率、疾病稳定率的差异无统计学意义;3／4级血液学毒性TPT高于紫杉醇,对铂类耐药者TPT的生存时间长于紫杉醇,差异有统计学意义;两者生存质量差异无统计学意义。②TPT与PLD比较:临床受益率、缓解率差异无统计学意义。3／4级血液学毒性,TPT高于PLD,差异有统计学意义。对铂类敏感者TPT组的生存时间短于PLD组:1年生存率差异无统计学意义;2、3年生存率TPT低于PLD,差异有统计学意义。成本效果分析:TPT的治疗总成本高于PLD;二者生活质量差异无统计学意义。③TPT两种用药剂量(方案)的比较:标准方案的缓解率及3／4级中性粒细胞减少的血液学毒性均大于24 h静滴方案;生存时间差异无统计学意义。④TPT口服与静脉两种用药途径相比:总缓解率静脉途径大于口服途径;口服途径的中性粒细胞减少的血液学毒性小于静脉途径,生存时间短于静脉途径。结论在ROC的化疗中,TPT的疗效优于紫杉醇,与PLD相当(TPT的临床受益率大于紫杉醇,缓解率相当于紫杉醇,对铂类耐药ROC患者TPT治疗的生存率大于紫杉醇)。TPT的缓解率和临床受益率与PLD差异无统计学意义,TPT的2、3年生存率低于PLD,铂类敏感的生存时间小于PLD;血液学毒性TPT大于紫杉醇和PLD;治疗成本TPT高于PLD。关于TPT在ROC的二线化疗中的临床应用,推荐用于耐药性、难治性的卵巢癌,选用治疗效果足够、毒性可以耐受的5天静脉滴注的标准治疗方案。

Topotecan for Recurrent Ovarian Cancer: A Systemic Review

Objective To assess the clinical efficacy, safety and cost-effectiveness of topotecan for recurrent epithelial ovarian cancer. Methods We searched MEDLINE (1966 to 2005), EMbase (1989 to 2004), CancerLit (1996 to 2003), CBMdisc (1978 to 2005), CNKI (1994 to 2005), The Cochrane Library (Issue 3,2005), The National Research Register, and the Health Technology Assessment Database (HTA). Relevant journals were also handsearched. The search was conducted on December 31, 2005. Randomize controlled trials (RCTs) comparing topotecan versus other agents for recurrent epithelial ovarian cancer were included. The quality of the eligible trials was assessed by two reviewers independently. Meta-analysis was performed. Results Four RCTs met the inclusion criteria, and the methodological quality was either level A or B. When used as second-line chemotherapy for recurrent ovarian cancer, there was no significant difference in remission rate between topotecan and paclitaxel or pegylated liposomal doxorubicin (PLD). The clinical benefit rate of topotecan was higher than that of paclitaxel or PLD. Myelosuppression was more frequent in patients in the topotecan group than those in the PLD or paclitaxel group, but it was not severe. As to cost-effectiveness analysis, topotecan was better than PLD. Conclusions The standard regimen of topotecan (intravenous 1.5 mg/m2/d for 5 consecutive days) is recommended for use in platinum-resistant and refractory ovarian cancer.