阿帕替尼联合化疗在铂类敏感复发性卵巢癌患者中的疗效及安全性评价

Evaluation of the efficacy and safety of apatinib combined with chemotherapy in patients with platinum-sensitive recurrent ovarian cancer

目的 观察阿帕替尼联合多柔比星脂质体和顺铂方案化疗在铂类敏感复发性卵巢癌患者中的疗效以及药物不良反应。方法 选取我院2017年1月—2019年6月收治的84例铂类敏感复发性卵巢癌患者,采用随机数字分组法分为对照组和观察组,每组42例。对照组给予贝伐珠单抗联合多柔比星脂质体和顺铂化疗,观察组给予阿帕替尼联合多柔比星脂质体和顺铂化疗。主要研究终点:客观有效率(ORR)、疾病控制率(DCR)、中位总生存期(mOS)和中位无进展生存期(mPFS);次要研究终点:腹水定量,血清人附睾蛋白4(HE4)、糖类抗原125(CA125)、血管内皮生长因子(VEGF)水平的变化,以及药物不良反应发生率。结果 治疗后,观察组患者实体瘤ORR、DCR分别为50.00%、78.57%,高于对照组的26.19%、57.14%(χ2=5.048,P=0.025;χ2=4.421,P=0.036)。观察组患者腹水总缓解率为71.43%,高于对照组的50.00%(χ2=4.043,P=0.044)。观察组患者血清HE4、CA125和VEGF水平低于对照组(t=8.136,P=0.019;t=7.351,P=0.024;t=9.311,P=0.014)。两组患者胃肠道反应、骨髓抑制和肝肾功能损伤发生率相比较,差异无统计学意义(χ2=0.207,P=0.649;χ2=0.762,P=0.383;χ2=0.454,P=0.500)。观察组患者手足综合征、高血压和口腔黏膜炎发生率高于对照组(χ2=4.141,P=0.042;χ2=6.891,P=0.009;χ2=6.574,P=0.010)。观察组患者mOS为17.5个月,mPFS为15.0个月,分别高于对照组患者的14.2个月和10.1个月(χ2=8.623,P=0.012;χ2=9.758,P=0.009)。结论 阿帕替尼联合多柔比星脂质体和顺铂方案化疗,在铂类敏感复发性卵巢癌患者中的疗效肯定,可延长其生存期,且不良反应可耐受,值得临床推广。

Objective To observe the efficacy and adverse drug reactions of apatinib combined with doxorubicin liposome and cisplatin chemotherapy in patients with platinum-sensitive recurrent ovarian cancer.Methods A total of 84 patients with platinum-sensitive recurrent ovarian cancer who were treated in our hospital between January 2017 and June2019 were selected and randomly divided into control group and observation group,42 cases in each group.The control group was given bevacizumab combined with doxorubicin liposome and cisplatin chemotherapy,and the observation group was given apatinib combined with doxorubicin liposome and cisplatin chemotherapy.The primary study endpoint:objective response rate(ORR),disease control rate(DCR),median overall survival(mOS),and median progression-free survival(mPFS).The secondary endpoint:quantitative ascites,changes of the serum levels of human epididymis protein 4(HE4),carbohydrate antigen 125(CA125) and vascular endothelial growth factor(VEGF),and incidence of adverse drug reactions.Results After treatment,the ORR and DCR of the observation group were 50.00% and 78.57% respectively,and both were higher than those of the control group(26.19% and 57.14%)(χ2=5.048,P=0.025;χ2=4.421,P=0.036).The total remission rate of ascites was higher in the observation group(71.43%) than in the control group(50.00%)(χ2=4.043,P=0.044).After treatment,the serum levels of HE4,CA125 and VEGF in the observation group were lower than those in the control group(t=8.136,P=0.019;t=7.351,P=0.024;t=9.311,P=0.014).No significant differences were found in the incidences of gastrointestinal reactions,bone marrow suppression and liver and kidney function injury between the two groups(χ2=0.207,P=0.649;χ2=0.762,P=0.383;χ2=0.454,P=0.500).However,the observation group had higher incidences of hand-foot syndrome,hypertension and oral mucositis than the control group(χ2=4.141,P=0.042;χ2=6.891,P=0.009;χ2=6.574,P=0.010).The observation group had mOS of 17.5 months and mPFS of 15.0 months,which were longer than those of the control group(respectively 14.2 and 10.1 months)(χ2=8.623,P=0.012;χ2=9.758,P=0.009).Conclusion Apatinib combined with doxorubicin liposome and cisplatin chemotherapy had a positive effect on patients with platinum-sensitive recurrent ovarian cancer.It could prolong the survival of patients,and its adverse reactions could be tolerated,so it is worthy of clinical promotion.