阿帕替尼治疗乙型病毒性肝炎相关性晚期肝细胞癌的疗效观察

Effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B

目的观察阿帕替尼治疗乙型病毒性肝炎相关性晚期肝细胞癌的临床疗效。方法回顾性分析2015年1月至2017年5月蚌埠医学院第一附属医院收治的72例乙型病毒性肝炎相关性晚期肝细胞癌患者的临床资料,其中37例患者口服阿帕替尼治疗,为阿帕替尼组,35例患者应用FOLFOX4方案(奥沙利铂+亚叶酸钙+5-氟尿嘧啶)姑息性化疗,为FOLFOX4组。比较两组患者的客观缓解率、疾病控制率、血清甲胎蛋白变化、临床症状改善率、Karnofsky功能状态(KPS)评分改善率、中位无进展生存期、中位总生存期及不良反应发生率。结果阿帕替尼组患者的客观缓解率为27.03%(10/37),高于FOLFOX4组的17.14%(6/35),但差异无统计学意义(χ^2=1.017,P=0.313);阿帕替尼组患者的疾病控制率为64.86%(24/37),高于FOLFOX4组的48.57%(17/35),但差异无统计学意义(χ^2=1.948,P=0.163)。治疗16周后,阿帕替尼组患者的血清甲胎蛋白水平为(280±20)ng/ml,显著低于FOLFOX4组的(450±20)ng/ml,差异有统计学意义(t=36.049,P<0.001);阿帕替尼组患者的KPS评分改善率为86.49%(32/37),明显优于FOLFOX4组的57.14%(20/35),差异有统计学意义(χ^2=7.720,P=0.006);阿帕替尼组患者的临床症状改善率为72.97%(27/37),明显优于FOLFOX4组的42.86%(15/35),差异有统计学意义(χ^2=6.712,P=0.010)。阿帕替尼组患者的中位无进展生存期为6.2个月,较FOLFOX4组的2.8个月明显延长,差异有统计学意义(χ^2=4.815,P=0.028);阿帕替尼组患者的中位总生存期为10.9个月,较FOLFOX4组的6.6个月明显延长,差异有统计学意义(χ^2=26.429,P<0.001)。阿帕替尼的不良反应主要为高血压、蛋白尿及手足综合征,FOLFOX4方案的不良反应主要为白细胞减少、神经毒性及肝功能损害;两组不良反应多数为1或2级,给予对症治疗后得到缓解和改善。结论阿帕替尼治疗乙型病毒性肝炎相关性晚期肝细胞癌安全有效,能够明显延长患者的生存期,明显提高患者生命质量和改善其临床症状。

ObjectiveTo observe the effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B.MethodsThe clinical data of 72 patients with advanced hepatocellular carcinoma associated with hepatitis B admitted to the First Affiliated Hospital of Bengbu Medical College from January 2015 to May 2017 were retrospectively analyzed.Among them,37 patients were treated with apatinib once a day,as apatinib group;35 patients were treated with FOLFOX4(oxaliplatin+calcium folinate+5-fluorouracil)palliative chemotherapy,as FOLFOX4 group.The objective response rate(ORR),disease control rate(DCR),serum alpha fetal protein(AFP),improvement of clinical symptoms,Karnofsky functional status(KPS)score improvement rate,median progression-free survival(PFS),median overall survival(OS),and the incidence of adverse reactions from both groups were contrastively analyzed.ResultsThe ORR of apatinib group(27.03%,10/37)was higher than that of FOLFOX4 group(17.14%,6/35),and DCR(64.86%,24/37)was also higher than that of FOLFOX4 group(48.57%,17/35).However,there were no significant difference in ORR and DCR between the two groups(χ^2=1.017,P=0.313;χ^2=1.948,P=0.163).After 16 weeks of treatment,serum AFP of apatinib group[(280±20)ng/ml]was significantly lower than that in FOLFOX4 group[(450±20)ng/ml,t=36.049,P<0.001].Improvement rate of KPS score(86.49%,32/37)was significantly more than that of FOLFOX4 group(57.14%,20/35;χ^2=7.720,P=0.006).Improvement rate of clinical symptoms(72.97%,27/37)was significantly more than that of FOLFOX4 group(42.86%,15/35;χ^2=6.712,P=0.010).The mean PFS of apatinib group was 6.2 months,which was significantly longer than that of FOLFOX4 group(2.8 months,χ^2=4.815,P=0.028).The mean OS of apatinib group was 10.9 months,which was significantly longer than that of FOLFOX4 group(6.6 months,χ^2=26.429,P<0.001).In apatinib group,the main adverse reactions were hypertension,proteinuria and hand-foot syndrome;and in FOLFOX4 group,the main adverse reactions were leukopenia,neurotoxicity and liver function damage.Moreover,the adverse reactions in both groups were mostly 1 or 2 grade,which could be relieved or improved through symptomatic treatment.ConclusionApatinib is safe and effective in the treatment of advanced hepatocellular carcinoma associated with hepatitis B.It can significantly prolong the life of patients and improve the quality of life and the clinical symptoms of patients.