| Objective: The aim of the study was to evaluate the curative effect of antagonizing vascular endothelial growth factor receptor drugs for patients with advanced gastric cancer.Methods: Searched Cochrane Library(Issue 12,2016),ClinicalTrails.gov,PubMed,Embase,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biological Medical Database,Wanfang Database and VIP Chinese Science & Technology Journal Database from inception to December 2016,to collect domestic and abroad published randomized controlled trials(RCTs)about antagonizing vascular endothelial growth factor receptor drugs for patients with advanced gastric cancer.Two reviewers solely sifted literatures out,abstracted data and rated quality of studies by the Cochrane handbook 5.1.Meta-analysis was implemented using RevMan 5.3 logiciel.Results: Ten studies containing 1 814 patients were comprised,of which they were RCTs.Meta-analysis results indicated that antagonizing vascular endothelial growth factor receptor(anti-VEGFR)drugs bonded with or without chemotherapy group(the anti-VEGFR drugs group)was better than the chemotherapy alone or placebo group(the control group)in overall survival(HR=0.77,95%CI 0.63 to 0.93,P=0.006),partial response(OR=1.58,95%CI 1.21 to 2.08,P=0.000 9),progression-free survival(HR=0.53,95%CI 0.38 to 0.73,P=0.000 1),disease control rate(OR=2.74,95%CI 1.88 to 3.98,P<0.000 01),objective response rate(OR=1.83,95%CI 1.41 to 2.38,P<0.000 01)and the reduction of progressive disease(OR=0.46,95%CI 0.35 to 0.60,P<0.000 01),but there were no differences in complete response(OR=1.69,95%CI 0.93 to 3.07,P=0.08)and stable disease(OR=1.72,95%CI 0.98 to 3.03,P=0.06).Subgroup analyses results are as follows:(1)In overall survival respect,the anti-VEGFR drugs group was more effective than the control group,which patients were ECOG PS ?1(P=0.000 4),up to two metastatic sites(P=0.000 2),age(years)<65(P=0.001)and age(years)?65(P=0.04),while there were no obvious differences in two groups,which patients were ECOG PS 0(P=0.06)and more than three metastatic sites(P=0.05).(2)In overall survival respect,the anti-VEGFR drugs group was more ranking than the control group,which patients were ECOG PS 0(P=0.001)and ? 1(P=0.001),gastric(P=0.000 2)and gastroesophageal junction adenocarcinoma(P=0.002),age(years)<65(P=0.02)and weight loss of less 10%(P=0.003),while there were no differences in two groups,which patients were age(years)?65(P=0.06)and weight loss of more 10%(P=0.33).(3)In terms of complete remission,there were no statistical meanings between Apatinib group and the control group(P=0.09),Ramucirumab group and the control group(P=0.55),Apatinib and S-1 group(P=1.00),the anti-VEGFR drugs group and placebo group(P=0.31),Ramucirumab combined with chemotherapy group and chemotherapy alone(P=0.58).(4)In partial remission respect,Ramucirumab group was better than the control group(P=0.004),while there were no statistical differences between Apatinib group and the control group(P=0.09),Apatinib and S-1 group(P=0.17),the anti-VEGFR drugs group and placebo group(P=0.41),Ramucirumab combined with chemotherapy group and chemotherapy alone(P=0.39).(5)In terms of stable disease,there showed statistically noteworthy differences between Ramucirumab group and the control group(P=0.04),the anti-VEGFR drugs group and placebo group(P<0.000 01),while there were no statistical differences between Apatinib group and the control group(P=0.58),Apatinib and S-1 group(P=0.32),Ramucirumab combined with chemotherapy group and chemotherapy alone(P=0.18).(6)In progressive disease respect,there displayed obviously statistically differences between Ramucirumab group and the control group(P<0.000 01),Ramucirumab combined with chemotherapy group and chemotherapy alone(P<0.000 01),while there were no differences between Apatnib group and the control group(P=0.47),Apatinib and S-1 group(P=0.67).(7)In terms of objective response rate,there were dramatically statistical significances between Apatnib group and the control group(P=0.000 3),the anti-VEGFR drugs group and placebo group(P=0.008),but there were no evidently differences between Ramucirumab group and the control group(P=0.19),Apatinib group and S-1 group(P=0.17),Ramucirumab combined with chemotherapy group and chemotherapy alone(P=0.33).(8)In disease control rate respect,there showed statistical differences between all subgroup(P=0.03,P<0.000 01,P<0.000 01,P<0.000 01),except difference between Apatinib and S-1 group(P=0.67).In terms of safety,compared with the control group,the occurrence of fatigue(OR=1.30,95%CI 1.05 to 1.61,P=0.02),thrombocytopenia(OR=2.38,95%CI 1.68 to 3.36,P<0.000 01),hypertension(OR=5.69,95%CI 3.30 to 9.83,P<0.000 01),hypoproteinemia(OR=2.08,95%CI 1.27 to 3.42,P=0.004)and proteinuria(OR=3.84,95%CI 2.69 to 5.47,P<0.000 01)in the anti-VEGFR drugs group were increased.However,other complications were no noteworthy differences in two groups.Meanwhile,the analyses results of ?3 adverse reactions showed that the incidence of diarrhea(OR=2.17,95%CI 1.07 to 4.41,P=0.03),hand-foot syndrome(OR=14.89,95%CI 3.37 to 65.72,P=0.000 4),proteinuria(OR=4.59,95%CI 1.19 to 17.74,P=0.03)and hypertension(OR=5.57,95%CI 3.21 to 9.68,P<0.000 01)in the anti-VEGFR drugs group were higher than control group,nevertheless the differences of other ?3 complications were no differences.Conclusion: Anti-VEGFR drugs in the treatment of patients with advanced gastric cancer not only can signally improve overall survival and progression-free survival,and improve the effective rate of treatment,but it may bring survival benefit and curative effect to the special subgroup of patients.However,it could aggrandize the incidence of fatigue,hypertension,thrombopenia,proteinuria and hypoproteinemia,especially,the incidence of grade 3 or higher diarrhea,hand-foot syndrome,hypertension and proteinuria.Due to the confined quality and quantity of the comprised studies,the above conclusion wants to be validated by proceeding more clinical studies. |
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