阿帕替尼联合白蛋白结合型紫杉醇治疗老年复发转移性胃癌的疗效及安全性评价

doi:10.3760/cma.j.cn371439-20200406-00098

摘要/Abstract

摘要：

目的观察阿帕替尼联合白蛋白结合型紫杉醇在老年复发转移性胃癌患者中的临床疗效及不良反应。方法选择中国科学技术大学附属第一医院西区肿瘤内科2017年6月1日至2019年6月1日确诊的72例老年复发转移性胃癌患者,采用随机数字表法分为对照组(n=36)和研究组(n=36)。对照组仅接受白蛋白结合型紫杉醇方案化疗,研究组在对照组化疗方案的基础上持续口服阿帕替尼,每3周为1个化疗周期,共4个周期。比较两组患者近期疗效、中位总生存期(OS)、中位无进展生存期(PFS),血清癌胚抗原(CEA)、糖类抗原199(CA199)、糖类抗原72-4(CA72-4)变化及不良反应发生情况。结果研究组患者客观有效率、疾病控制率分别为55.56%(20/36)、77.78%(28/36),高于对照组的30.56%(11/36)、55.56%(20/36),差异均有统计学意义(χ²=4.589,P=0.032;χ²=4.000,P=0.046)。治疗4个周期后,研究组患者血清CEA、CA199、CA72-4水平分别为(12.5±3.3)μg/L、(35.6±6.7)U/ml、(13.5±2.2)U/ml,均低于对照组的(22.8±4.1)μg/L、(55.6±7.4)U/ml、(21.7±3.4)U/ml,差异均具有统计学意义(t=7.008,P=0.017;t=9.365,P=0.008;t=8.862,P=0.011)。研究组患者胃肠反应发生率为38.89%(14/36)、骨髓抑制发生率为44.44%(16/36),对照组分别为36.11%(13/36)、41.67%(15/36),差异均无统计学意义(χ²=0.059,P=0.808;χ²=0.057,P=0.811);研究组患者高血压、手足综合征、口腔黏膜炎和蛋白尿发生率分别为27.78%(10/36)、41.67%(15/36)、27.78%(10/36)和16.67%(6/36),均高于对照组的8.33%(3/36)、16.67%(6/36)、5.56%(2/36)和2.78%(1/36),差异均具有统计学意义(χ²=4.600,P=0.032;χ²=5.445,P=0.020;χ²=6.400,P=0.011;χ²=3.956,P=0.047),经对症处理后均可耐受。研究组患者的中位OS、中位PFS分别为18.2个月和16.1个月,均长于对照组的11.8个月和8.0个月,差异均具有统计学意义(χ²=6.821,P=0.015;χ²=5.868,P=0.018)。结论阿帕替尼联合白蛋白结合型紫杉醇在老年复发转移性胃癌患者中的疗效优于白蛋白结合型紫杉醇单药化疗,可延长PFS和OS,不良反应可耐受。

关键词: 胃肿瘤, 白蛋白结合型紫杉醇, 肿瘤转移, 复发, 阿帕替尼

Abstract:

Objective To observe the clinical efficacy and adverse reactions of apatinib combined with albumin-bound paclitaxel in elderly patients with relapsed and metastatic gastric cancer. Methods A total of 72 elderly patients with relapsed and metastatic gastric cancer diagnosed in the Department of Oncology, West District of the First Affiliated Hospital of University of Science & Technology of China from June 1, 2017 to June 1, 2019 were chosen. The patients were divided into control group (n=36) and study group (n=36) using random number table method. The control group received only albumin-bound paclitaxel chemotherapy, and the study group continued oral apatinib based on the control group's chemotherapy, every 3 weeks for one chemotherapy cycle, a total of 4 cycles. The short-term efficacy, median overall survival (OS), median progression-free survival (PFS), serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 72-4 (CA72-4) and adverse reactions were compared between the two groups. Results The objective response rate and disease control rate of the study group were 55.56% (20/36) and 77.78% (28/36) respectively, which were higher than those of the control group [30.56% (11/36) and 55.56% (20/36)], and there were statistically significant differences (χ²=4.589, P=0.032; χ²=4.000, P=0.046). After 4 cycles treatment, the serum CEA, CA199 and CA72-4 levels in the study group were (12.5±3.3) μg/L, (35.6±6.7) U/ml, (13.5±2.2) U/ml respectively, which were lower than those in the control group [(22.8±4.1) μg/L, (55.6±7.4) U/ml, (21.7±3.4) U/ml], and there were statistically significant differences (t=7.008, P=0.017; t=9.365, P=0.008; t=8.862, P=0.011). The incidences of gastrointestinal reactions and myelosuppression were 38.89% (14/36) and 44.44% (16/36) in the study group, and 36.11% (13/36) and 41.67% (15/36) in the control group respectively, with no significant differences (χ²=0.059, P=0.808; χ²=0.057, P=0.811). The incidences of hypertension, hand-foot syndrome, oral mucositis and proteinuria in the study group were 27.78% (10/36), 41.67% (15/36), 27.78% (10/36) and 16.67% (6/36) respectively, which were higher than those in the control group [8.33% (3/36), 16.67% (6/36), 5.56% (2/36) and 2.78% (1/36)], and there were statistically significant differences (χ²=4.600, P=0.032; χ²=5.445, P=0.020; χ²=6.400, P=0.011; χ²=3.956, P=0.047), which could be tolerated after symptomatic treatment. The median OS and PFS of the study group were 18.2 months and 16.1 months, which were longer than those of the control group (11.8 months and 8.0 months), and there were statistically significant differences (χ²=6.821, P=0.015; χ²=5.868, P=0.018). Conclusion Apatinib combined with albumin-bound paclitaxel is superior to albumin-bound paclitaxel single-agent chemotherapy in elderly patients with relapsed and metastatic gastric cancer, which can prolong the PFS and OS, and the adverse reactions are tolerable.

Key words: Stomach neoplasms, Albumin-bound paclitaxel, Neoplasm metastasis, Recurrence, Apatinib

高爽, 胡长路. 阿帕替尼联合白蛋白结合型紫杉醇治疗老年复发转移性胃癌的疗效及安全性评价[J]. 国际肿瘤学杂志, 2020, 47(11): 669-674.

Gao Shuang, Hu Changlu. Efficacy and safety evaluation of apatinib combined with albumin-bound paclitaxel in the treatment of elderly patients with relapsed and metastatic gastric cancer[J]. Journal of International Oncology, 2020, 47(11): 669-674.

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临床病理资料	对照组 (n=36)	研究组 (n=36)	χ²值	P值
性别
男	21	19	0.225	0.635
女	15	17
复发或转移位置
吻合口	4	3
肺	5	6
肝脏	8	11	1.010	0.908
区域淋巴结	10	9
2处及以上	9	7
以往治疗情况
单纯根治手术	7	9	0.321	0.571
根治性手术及术后辅助化疗	29	27
分化程度
高分化	5	4
中分化	23	25	0.261	0.878
低分化	8	7

组别	CR	PR	SD	PD	客观有效	疾病控制
对照组(n=36)	0(0)	11(30.56)	9(25.00)	16(44.44)	11(30.56)	20(55.56)
研究组(n=36)	1(2.78)	19(52.78)	8(22.22)	8(22.22)	20(55.56)	28(77.78)
χ²值					4.589	4.000
P值					0.032	0.046

组别	CEA(μg/L)		CA199(U/ml)		CA72-4(U/ml)
组别	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组(n=36)	35.1±6.3	22.8±4.1	63.8±8.5	55.6±7.4	22.9±3.5	21.7±3.4
研究组(n=36)	33.6±5.5	12.5±3.3	61.2±7.4	35.6±6.7	20.6±3.6	13.5±2.2
t值	1.834	7.008	2.325	9.365	2.683	8.862
P值	0.259	0.017	0.236	0.008	0.126	0.011