伊马替尼治疗不能切除和(或)转移性胃肠道间质瘤的系统评价

摘要

目的 系统评价伊马替尼治疗不能切除和(或)转移性胃肠道间质瘤的有效性和安全性.方法 计算机检索PubMed(1989～2009.4)、EMbase(1989～2009.4)、Cochrane 图书馆(2009 年第3期)、CBM(1989～2009.4)、CNKI(1989～2009.4)、VIP(1989～2009.4).同时手工检索其引文,以便发现新的可纳入文献.按Cochrane 协作网推荐的方法进行系统评价.结果 共纳入5个RCT,包括1 845例患者.meta 分析结果显示:与标准剂量组(400 mg/d)相比,高剂量组(600 mg/d或800 mg/d)依马替尼虽然增加2年无疾病进展生存率[RR=1.15,95% CI=1.01~1.30,P=0.03],但在2年总生存率(RR=1.00,95% CI=0.92～1.08,P=0.93)、完全肿瘤反应率(RR=1.02,95% CI=0.66～1.59,P=0.93)、部分肿瘤反应率(RR=1.06,95% CI=0.96～1.17,P=0.28)方面两组相似.在安全性方面,高剂量组依马替尼增加了血液毒性反应(RR=1.08,95% CI=1.03～1.14,P=0.003)和各种非血液毒性反应(RR:1.18～2.07,95% CI =1.06～3.32,P均＜0.05),特别是增加了3级以上毒性反应(RR=1.48,95% CI=1.33～1.65,P＜0.00001).依马替尼间断治疗的患者出现疾病进展的风险明显增高(RR=0.27,95% CI=0.13～0.58,P＜0.05),而生存质量未见改善(MD=3.50,95% CI=-11.17～18.17,P＞0.05).结论 对不能切除和(或)转移性的胃肠道间质瘤患者,增加剂量,病人未见明显临床获益;依马替尼治疗胃肠道间质瘤取得疗效后,应持续服药,以免引起疾病进展的风险增加.%Objective To systematically review the efficacy and safety of Imatinib treatment for patients with unresectable and/or metastatic gastrointestinal stromal tumours. Methods Pubmed ( 1989 to April 2009) , EMbase ( 1989 to April 2009), the Cochrane library ( Issue 3, 2009) , CBM ( 1989 to April 2009), CNKI ( 1989 to April 2009), VIP ( 1989 to April 2009) were searched electronically. In order to include in the new literature, their citations were handsearched. The quality of included randomized controlled trals (RCTs) was evaluated and meta-analysis was conducted by RevMan 5.0. Results Five RCTs, including 1 845 cases of patients, were identified. Results of meta analysis showed that: compared to the standard dose of imatinib (400 mg/d) group, high-dose of imatinib (600 mg/d or 800 mg/d) group increased 2 years progression-free survival ( RR = 1.15, 95％ CI = 1.01 ～ 1.30, P = 0.03 ) , but the 2 years overall survival rate (RR = 1.00, 95％ CI =0.92～ 1.08, P=0.93), complete tumor response rate (RR =1.02, 95％ CI=0.66 ～1.59, P=0.93), part of tumor response rate (RR=l.06, 95％ CI=0.96～1.17, P=0.28) had no significantly difference between the two groups. In safety, high-dose imatinib group increased blood toxicity (RR = 1.08, 95％ CI = 1.03 ～ 1.14, P =0.003) and a variety of non-blood toxicity (RR: 1.18 ～2.07,95％ CI =1.06 ～ 3.32, P ＜ 0.05). In particular, increased the severe ( higher than 3 grade) toxicity ( RR = 1.48, 95％ CI =1.33～ 1.65, P ＜0. 00001 ). Intermittent imatinib treatment could not reduce the risk of disease progression (RR =0.27, 95％ CI=0.13 ～0.58, P＜0.05), the quality of life was not improving as well (MD =3.50, 95％CI =- 11.17 ～ 18.17, P ＞ 0.05 ). Conclusion For patients with unresectable and/or metastatic GISTs, increased the dose of imatinib could not get more clinical benefit. When the treatment effect achieved, Imatinib should be maintain to avoid increasing the risk of disease progression.