Risk Factors Of Secondary Hypertension Induced By Advanced Gastric Cancer Treated With Apatinib

Objective: To observe the clinical efficacy and adverse reactions of apatinib for advanced gastric cancer,and explore the risk factors of secondary hypertension induced by apatinib.Methods: 38 patients with advanced gastric cancer treated with apatinib in the Renmin Hospital,Hubei University of Medicine were followed up to evaluate the clinical efficacy and adverse reactions of apatinib for advanced gastric cancer.All the patients were orally administrated with apatinib(0.25 g/d)until the disease progressed,died or intolerable.Progression free survival(PFS),clinical efficacy and adverse events were observed and recorded.The Kaplan-Meier method was used to detect important factors that may affect the PFS of the patients.The risk factors for the occurrence of hypertension were evaluated by using univariate and Logistic regression analysis model.Results:1.Clinical efficacy: 12 patients achieved a partial response(PR),17 patients achieved a stable disease(SD)and 9 patients achieved a progressive disease(PD)within those patients.The objective response rate(ORR)was31.6% and the disease control rate(DCR)was 76.3%.2.Survival analysis and influencing factors: 5 patients died before the disease progressed and 4 patients were lost during the follow-up period by December 31,2018.The censoring rate was 10.5%.The m PFS of 38 patients was 3.640 months(95%CI: 2.947-4.333)and the m PFS of the hypertension group was superior to the normotensive group(3.920 months,95%CI:3.332-4.508 VS 3.030 months,95%CI: 2.797-3.263;P=0.002<0.05).The m PFS in adenocarcinoma alone was superior to adenocarcinoma in combination with other types(3.740 months,95%CI: 3.610-3.870 VS 2.490 months,95%CI: 1.156-3.824;P = 0.000 < 0.05).3.Adverse reactions mainly included hypertension,symptoms of hand-foot syndrome,nausea and vomiting,proteinuria,fatigue,diarrhea,bonemarrow suppression.Hypertension occurred in 16 patients(42.1%),including14(36.8%)grade I-II cases and 2(5.3%)grade III-IV cases.12 patients had symptoms of hand-foot syndrome(31.6%),all of which were grade I-II.5patients(13.2%)had nausea and vomiting,all of which were grade I.Proteinuria(grade I-II)occurred in 4 patients(10.5%).6 patients(15.8%)had fatigue,including 5(13.2%)grade I-II cases and 1(2.6%)grade III-IV cases.Moreover,diarrhea(grade I)in 3 patients and myelosuppression(grade I-II)in7 patients were found.In most patients,the adverse reactions were mild,and the symptoms were relieved after symptomatic treatment.Two patients with grade 3 hypertension were not relieved after antihypertensive treatment.With the assistance of cardiology,the symptoms were relieved after the temporary drug.4.Analysis of risk factors: Hypertension occurred in 16 patients(42.1%),including 14(36.8%)grade I-II cases and 2(5.3%)grade III-IV cases,without hypertension crisis.The age,history of smoking and ECOG scores of patients were found to be associated with secondary hypertension induced by apatinib(P<0.05)by univariate analysis.Logistic regression analysis showed that age(OR=1.823,95% CI: 1.097-3.053)was an independent risk factor for the treatment of advanced gastric cancer with apatinib(P<0.05).Conclusion:1.The adverse effects of apatinib are controllable and the patient is well tolerated.Apatinib is an effective treatment for patients with advanced gastric cancer who have failed in the second or second-line standard regimen and can be used for the maintenance treatment of those patients.2.PFS of patients with advanced gastric cancer treated with apatinib depended on the type of pathology the patients were and whether secondary hypertension the patients had.3.Age is the independent risk factor of secondary hypertension induced by apatinib.