阿帕替尼联合放化疗对晚期胃癌疗效及肿瘤标志物的影响

doi:10.3760/cma.j.cn371439-20210610-00118

摘要/Abstract

摘要：

目的观察阿帕替尼联合放化疗方案治疗晚期胃癌的近、远期疗效及对肿瘤标志物的影响。方法选取2013年1月至2017年1月西安市长安医院肿瘤科收治的84例晚期胃癌患者为研究对象,采用前瞻性巢式对照研究法将患者分为同步放化疗组和靶向放化疗组,每组42例。同步放化疗组接受同步放化疗治疗方案治疗,靶向放化疗组接受阿帕替尼联合放化疗方案治疗,2周为1个周期,共12个周期。比较两组患者的近期和远期疗效、中位总生存期及胃癌相关标志物变化及不良反应发生情况。结果治疗3个月后,同步放化疗组和靶向放化疗组疗效分布差异无统计学意义(Z=0.240,P=0.887),两组患者的疾病控制率分别为69.05%(29/42)和73.81%(31/42),差异无统计学意义(χ²=0.233,P=0.629)。治疗6个月后,同步放化疗组和靶向放化疗组疗效分布差异具有统计学意义(Z=6.288,P=0.043),两组患者的疾病控制率分别为42.86%(18/42)和69.05%(29/42),差异具有统计学意义(χ²=5.845,P=0.016)。靶向放化疗组和同步放化疗组的中位总生存期分别为18.7个月(95%CI为8.4~24.8)和13.8个月(95%CI为7.2~18.7),差异具有统计学意义(χ²=7.542,P<0.001)。治疗3个月后,靶向放化疗组的糖类抗原(CA)19-9、CA125、癌胚抗原(CEA)分别为(16.27±2.13)U/ml、(13.25±2.26)U/ml、(2.97±0.85)ng/ml,同步放化疗组分别为(29.34±3.69)U/ml、(21.63±2.69)U/ml、(6.19±1.23)ng/ml,均较本组内治疗前降低,且治疗后靶向放化疗组的CA19-9、CA125、CEA均低于同步放化疗组,差异均具有统计学意义(t=19.880,P<0.001;t=15.458,P<0.001;t=13.957,P<0.001)。靶向放化疗组和同步放化疗组的3~4级不良反应总发生率分别为23.81%(10/42)和28.64%(12/42),差异无统计学意义(χ²=0.186,P=0.667)。结论阿帕替尼联合放化疗治疗晚期胃癌远期疗效优于同步放化疗,且安全可靠,同时可延长总生存期,降低血清肿瘤标志物水平。

关键词: 胃肿瘤, 放射疗法, 药物疗法, 生物标记, 阿帕替尼

Abstract:

Objective To observe the short- and long-term efficacy of apatinib combined with chemoradiotherapy in the treatment of advanced gastric cancer and its effect on tumor markers. Methods From January 2013 to January 2017, 84 patients with advanced gastric cancer admitted to the Department of Oncology of Chang'an Hospital of Xi'an City were selected as the subjects. The patients were divided into synchronous chemoradiotherapy group and targeted chemoradiotherapy group by prospective nested control method, with 42 cases in each group. The synchronous chemoradiotherapy group was treated with synchronous chemoradiotherapy, and the targeted chemoradiotherapy group was treated with apatinib combined with chemoradiotherapy, 2 weeks was a cycle, a total of 12 cycles. The short- and long-term efficacy, median overall survival, changes of gastric cancer-related markers and adverse reactions of the two groups were compared. Results After 3 months of treatment, there was no significant difference in the efficacy distribution between the synchronous chemoradiotherapy group and the targeted chemoradiotherapy group (Z=0.240, P=0.887). The disease control rates of the two groups were 69.05% (29/42) and 73.81% (31/42) respectively, with no statistically significant difference (χ²=0.233, P=0.629). After 6 months of treatment, the difference of the efficacy distribution between the synchronous chemoradiotherapy group and the targeted chemoradiotherapy group was statistically significant (Z=6.288, P=0.043), and the disease control rates of the two groups were 42.86% (18/42) and 69.05% (29/42) respectively, with a statistically significant difference (χ ²=5.845, P=0.016). The median overall survival in the targeted chemoradiotherapy group and synchronous chemoradiotherapy groups were 18.7 months (95%CI: 8.4-24.8) and 13.8 months (95%CI: 7.2-18.7), with a statistically significant difference (χ ²=7.542, P<0.001). After 3 months of treatment, the levels of carbohydrate antigen (CA) 19-9, CA125, carcino-embryonic antigen (CEA) were (16.27±2.13) U/ml, (13.25±2.26) U/ml, (2.97±0.85) ng/ml in the targeted chemoradiotherapy group and (29.34±3.69) U/ml, (21.63±2.69) U/ml, (6.19±1.23) ng/ml in the synchronous chemoradiotherapy group respectively, all of them were lower than those before treatment, and the CA19-9, CA125, CEA in the targeted chemoradiotherapy group were lower than those in the synchronous chemoradiotherapy group, and there were statistically significant differences (t=19.880, P<0.001; t=15.458, P<0.001; t=13.957, P<0.001). The total incidence of grade 3-4 adverse reactions in the targeted chemoradiotherapy group was 23.81% (10/42) and 28.64% (12/42) in the synchronous chemoradiotherapy group, and there was no statistically significant difference (χ ²=0.186, P=0.667). Conclusion The long-term efficacy of apatinib combined with chemoradiotherapy in the treatment of advanced gastric cancer is better than that of synchronous chemoradiotherapy, and it is safe and reliable. At the same time, it can prolong the overall survival and reduce the levels of serum tumor markers.

Key words: Stomach neoplasm, Radiotherapy, Drug therapy, Biomarkers, Apatinib

王旋, 崔立春, 党升强. 阿帕替尼联合放化疗对晚期胃癌疗效及肿瘤标志物的影响[J]. 国际肿瘤学杂志, 2021, 48(10): 602-607.

Wang Xuan, Cui Lichun, Dang Shengqiang. Effects of apatinib combined with chemoradiotherapy on the efficacy and tumor markers of advanced gastric cancer[J]. Journal of International Oncology, 2021, 48(10): 602-607.

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基本特征	同步放化疗组 (n=42)	靶向放化疗组 (n=42)	χ²/t值	P值
性别
男	22(52.38)	23(54.76)	0.048	0.827
女	20(47.62)	19(46.24)
年龄(岁)	56.83±4.82	56.71±4.92	0.113	0.910
体力状况评分(分)
0	24(57.14)	25(59.52)
1	12(28.57)	12(28.97)	0.111	0.946
2	6(14.29)	5(11.91)
主要转移部位
骨	4(9.52)	3(7.14)
肝	6(14.29)	7(16.67)	0.380	0.827
肾	2(4.73)	3(7.14)

组别	完全缓解	部分缓解	病情稳定	疾病进展	疾病控制
同步放化疗组(n=42)	0(0)	10(23.81)	19(45.24)	13(30.95)	29(69.05)
靶向放化疗组(n=42)	0(0)	11(26.19)	20(47.62)	11(26.19)	31(73.81)
Z/χ²值	0.240				0.233
P值	0.887				0.629

组别	完全缓解	部分缓解	病情稳定	疾病进展	疾病控制
同步放化疗组(n=42)	0(0)	6(14.29)	12(28.57)	24(57.14)	18(42.86)
靶向放化疗组(n=42)	0(0)	7(16.67)	22(52.38)	13(30.95)	29(69.05)
Z/χ²值	6.288				5.845
P值	0.043				0.016

组别	CA19-9(U/ml)		CA125(U/ml)		CEA(ng/ml)
组别	治疗前	治疗3个月	治疗前	治疗3个月	治疗前	治疗3个月
同步放化疗组(n=42)	56.82±10.12	29.34±3.69^a	47.46±5.97	21.63±2.69^a	16.28±2.24	6.19±1.23^a
靶向放化疗组(n=42)	56.66±10.28	16.27±2.13^a	47.12±5.88	13.25±2.26^a	16.78±2.12	2.97±0.85^a
t值	0.072	19.880	0.263	15.458	1.050	13.957
P值	0.943	<0.001	0.793	<0.001	0.297	<0.001

不良反应	同步放化疗组 (n=42)	靶向放化疗组 (n=42)
白细胞减少	3(7.14)	3(7.14)	<0.001	>0.999
中性线粒细胞减少	3(7.14)	4(9.52)	0.156	0.693
血小板减少	3(7.14)	3(7.14)	<0.001	>0.999
恶心、呕吐	1(2.38)	2(4.76)	0.346	0.556
合计	10(23.81)	12(28.64)	0.186	0.667