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

Imatinib treatment for the patients with unresectable and/or metastatic gastrointestinal stromal tumors:a systematic review

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 hand- searched. The quality of included randomized controlled trals （RCTs） was evaluated and meta-analysis was conducted by RevMan 5. O. 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 =1.06, 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.