阿帕替尼联合替吉奥在晚期食管癌中的临床疗效及安全性评价

Clinical efficacy and safety evaluation of apatinib combined with tegio in the treatment of advanced esophageal cancer

目的观察阿帕替尼联合替吉奥在晚期食管癌二线治疗中的临床疗效及药物不良反应。方法选取中国人民解放军联勤保障部队第九〇一医院肿瘤中心2018年1月至2019年12月收治的晚期食管癌患者72例作为研究对象,采用随机数字表法将患者分为对照组(n=36)和观察组(n=36)。对照组患者给予伊立替康联合替吉奥方案化疗,伊立替康160 mg/m^(2),第1天静脉滴注;替吉奥50~60 mg/次,2次/d,口服2周,停药1周,3周为1个周期。观察组患者的替吉奥给药方法和剂量同对照组,阿帕替尼0.5 g/次,1次/d,持续口服给药,3周为1个周期。两组患者均治疗4个周期。主要研究终点为客观缓解率(ORR)、疾病控制率(DCR),次要研究终点为中位总生存期(mOS)、中位无进展生存期(mPFS)、生命质量评分及药物不良反应发生率。结果治疗4个周期后,观察组患者ORR、DCR分别为38.89%(14/36)、63.89%(23/36),高于对照组的16.67%(6/36)、38.89%(14/36),差异均有统计学意义(χ^(2)=4.431,P=0.035;χ^(2)=4.503,P=0.034)。观察组患者Karnofsky功能状态评分、食管癌专用量表QLQ-OES24评分分别为(75.23±10.65)分、(76.55±9.12)分,高于对照组的(66.15±10.31)分、(65.36±9.01)分,差异均有统计学意义(t=7.285,P=0.018;t=7.613,P=0.015)。观察组患者口腔黏膜炎、手足综合征、高血压、蛋白尿、皮疹的发生率分别为38.89%(14/36)、50.00%(18/36)、25.00%(9/36)、11.11%(4/36)、33.33%(12/36),均高于对照组的11.11%(4/36)、13.89%(5/36)、0(0/36)、0(0/36)、2.78%(1/36),差异均有统计学意义(χ^(2)=7.407,P=0.007;χ^(2)=10.797,P=0.001;χ^(2)=10.286,P=0.001;χ^(2)=4.235,P=0.040;χ^(2)=11.359,P=0.001)。观察组患者胃肠反应、骨髓抑制发生率分别为41.67%(15/36)、30.56%(11/36),均低于对照组的66.67%(24/36)、55.56%(20/36),差异均有统计学意义(χ^(2)=4.531,P=0.033;χ^(2)=4.589,P=0.032)。无因严重不良反应退出的病例。观察组患者mOS、mPFS分别为11.6个月、8.1个月,长于对照组的8.9个月、5.6个月,差异均具有统计学意义(χ^(2)=8.015,P=0.012;χ^(2)=8.721,P=0.007)。结论阿帕替尼联合替吉奥在晚期食管癌患者二线治疗中可有效延长患者生存期,改善生命质量,不良反应可耐受。

Objective To observe the clinical efficacy and adverse drug reactions of apatinib combined with tegio in the second-line treatment of advanced esophageal cancer.Methods Seventy-two patients with advanced esophageal cancer from January 2018 to December 2019 in the Tumor Center of the No.901 Hospital of Chinese People′s Liberation Army Joint Logistics Support Force were selected as research objects.According to the random number table method,the patients were divided into control group(n=36)and observation group(n=36).Patients in the control group were given irinotecan combined with tegio regimen chemotherapy,irinotecan 160 mg/m^(2),intravenous drip on the first day;tegio 50-60 mg orally each time,twice a day,oral administration for 2 weeks,discontinuation for 1 week,3 weeks for 1 cycle.Patients in the observation group were given tegio with the same administration method and dosage as the control group,and apatinib 0.5 g orally each time,once a day,continuous oral administration,3 weeks for 1 cycle.Patients of the two groups were treated for 4 cycles.The primary study endpoints were objective response rate(ORR)and disease control rate(DCR).The secondary study endpoints were median overall survival(mOS),median progression-free survival(mPFS),quality of life scores and incidences of adverse drug reactions.Results After 4 cycles of treatment,the ORR and DCR in the observation group were 38.89%(14/36)and 63.89%(23/36)respectively,which were higher than those in the control group[16.67%(6/36)and 38.89%(14/36)],and there were statistically significant differences(χ^(2)=4.431,P=0.035;χ^(2)=4.503,P=0.034).The Karnofsky performance status score and special scale for esophageal cancer QLQ-OES24 score in the observation group were 75.23±10.65 and 76.55±9.12 respectively,which were higher than those in the control group(66.15±10.31 and 65.36±9.01),and there were statistically significant differences(t=7.285,P=0.018;t=7.613,P=0.015).The incidences of oral mucositis,hand-foot syndrome,hypertension,proteinuria and rash in the observation group were 38.89%(14/36),50.00%(18/36),25.00%(9/36),11.11%(4/36)and 33.33%(12/36)respectively,which were higher than those in the control group[11.11%(4/36),13.89%(5/36),0(0/36),0(0/36),2.78%(1/36)],and there were statistically significant differences(χ^(2)=7.407,P=0.007;χ^(2)=10.797,P=0.001;χ^(2)=10.286,P=0.001;χ^(2)=4.235,P=0.040;χ^(2)=11.359,P=0.001).The incidences of gastrointestinal reactions and bone marrow suppression in the observation group were 41.67%(15/36)and 30.56%(11/36)respectively,which were lower than those in the control group[66.67%(24/36)and 55.56%(20/36)],and there were statistically significant differences(χ^(2)=4.531,P=0.033;χ^(2)=4.589,P=0.032).There were no patients who withdrew due to severe adverse reactions.The mOS and mPFS of the patients in the observation group were 11.6 months and 8.1 months respectively,which were longer than those in the control group(8.9 months and 5.6 months),and there were statistically significant differences(χ^(2)=8.015,P=0.012;χ^(2)=8.721,P=0.007).Conclusion Apatinib combined with tegio in the second-line treatment of patients with advanced esophageal cancer can effectively prolong the survival time of patients,improve patients′quality of life,and the adverse reactions are tolerable.