安罗替尼治疗二线失败后老年小细胞肺癌患者的疗效及影响因素分析

摘要/Abstract

摘要：

目的探讨老年小细胞肺癌患者二线治疗失败后使用安罗替尼治疗的疗效及影响因素。方法收集2018年9月至2020年2月在新疆医科大学附属肿瘤医院确诊并接受治疗的老年小细胞肺癌患者共56例。所有患者均经过二线方案化疗失败后使用安罗替尼胶囊治疗,统计患者的客观缓解率(ORR)、疾病控制率(DCR)和无进展生存期(PFS)。比较不同临床特征患者的ORR、DCR和PFS。Cox比例风险模型分析老年小细胞肺癌患者PFS的影响因素,观察药物不良反应。结果56例老年小细胞肺癌患者治疗2个周期后ORR为10.7%(6/56),DCR为53.6%(30/56)。其中,不合并脑转移患者ORR为20.8%(5/24),DCR为75.0%(18/24),均高于合并脑转移患者的3.1%(1/32)、37.5%(12/32),差异均有统计学意义(χ²=4.496,P=0.034;χ²=7.754,P=0.005)。美国东部肿瘤协作组(ECOG)评分0~1分患者的ORR为21.7%(5/23),DCR为69.6%(16/23),均高于ECOG评分2~3分患者的3.0%(1/33),42.4%(14/33),差异均有统计学意义(χ²=4.959,P=0.026;χ²=4.014,P=0.045)。ORR及DCR与患者性别、年龄、临床分期、吸烟状况均无关(均P>0.05)。56例患者中位PFS为3.8个月,年龄≤70岁患者的中位PFS为5.0个月,年龄>70岁患者为3.4个月,差异有统计学意义(χ²=5.452,P=0.020)。不合并脑转移患者的中位PFS为5.1个月,合并脑转移患者为3.2个月,差异有统计学意义(χ²=8.895,P=0.003)。ECOG评分0~1分患者的中位PFS为5.0个月,ECOG评分2~3分患者为2.9个月,差异有统计学意义(χ²=5.923,P=0.015)。局限期患者的中位PFS为5.0个月,广泛期患者为3.1个月,差异有统计学意义(χ²=5.141,P=0.023)。Cox回归多因素分析显示,ECOG评分(HR=2.522,95%CI为1.378~4.615,P=0.003)、是否合并脑转移(HR=0.323,95%CI为0.168~0.622,P=0.001)是影响患者PFS的独立预后因素。安罗替尼治疗过程中主要为Ⅰ~Ⅱ级的不良反应,Ⅲ~Ⅳ级不良反应主要为高血压及手足综合征,给予药物减量及对症处理后好转,后续耐受可。药物减量发生率为3.6%(2/56),无药物中断和终止治疗患者。结论安罗替尼治疗二线失败后老年小细胞肺癌患者具有较好的近期疗效及生存获益,对ECOG评分低、不合并脑转移的患者治疗效果较好,不良反应可耐受,安全性高。

关键词:小细胞肺癌,老年人,安罗替尼,疗效分析,影响因素

Abstract:

ObjectiveTo investigate the efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure.MethodsA total of 56 elderly patients with small cell lung cancer who were diagnosed and treated in the Tumor Hospital Affiliated to Xinjiang Medical University from September 2018 to February 2020 were collected. All patients were treated with anlotinib capsule after failure of second-line chemotherapy, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were calculated, and ORR, DCR and PFS of patients with different clinical characteristics were compared. Cox proportional hazards model was used to analyze the factors influencing PFS in elderly patients with small cell lung cancer, and adverse drug reactions were observed.ResultsAfter 2 cycles of treatment, the ORR and DCR of 56 elderly patients with small cell lung cancer were 10.7% (6/56) and 53.6% (30/56) respectively. Among them, the ORR and DCR of patients without brain metastasis were 20.8% (5/24) and 75.0% (18/24), which were higher than 3.1% (1/32) and 37.5% (12/32) in patients with brain metastasis, with statistically significant differences (χ²=4.496,P=0.034;χ²=7.754,P=0.005). The ORR and DCR of patients with Eastern Cooperative Oncology Group (ECOG) score of 0-1 were 21.7% (5/23) and 69.6% (16/23), which were higher than those of patients with ECOG score of 2-3 [3.0% (1/33), 42.4% (14/33)], with statistically significant differences (χ²=4.959,P=0.026;χ²=4.014,P=0.045). ORR and DCR were not related to gender, age, clinical stage or smoking status (allP>0.05). The median PFS of 56 patients was 3.8 months. The median PFS of patients aged ≤70 years was 5.0 months, and that of patients aged >70 years was 3.4 months, with a statistically significant difference (χ²=5.452,P=0.020). The median PFS of patients without brain metastasis was 5.1 months, and that of patients with brain metastasis was 3.2 months, with a statistically significant difference (χ²=8.895,P=0.003). The median PFS of patients with ECOG score of 0-1 was 5.0 months, and that of patients with ECOG score of 2-3 was 2.9 months, with a statistically significant difference (χ²=5.923,P=0.015). The median PFS of patients with limited stage was 5.0 months, and that of patients with extensive stage was 3.1 months, with a statistically significant difference (χ²=5.141,P=0.023). Cox multivariate analysis showed that ECOG score (HR=2.522, 95%CI: 1.378-4.615,P=0.003) and brain metastasis or not (HR=0.323, 95%CI: 0.168-0.622,P=0.001) were independent prognostic factors of PFS. During the treatment of anlotinib, the main adverse reactions were grade Ⅰ-Ⅱ, grade Ⅲ-Ⅳ adverse reactions were mainly hypertension and hand-foot syndrome, which improved after drug reduction and symptomatic treatment, and could be tolerated later. The incidence of drug reduction was 3.6% (2/56), and there were no patients with drug interruption or termination of treatment.ConclusionAnlotinib has good short-term efficacy and survival benefits in the treatment of elderly patients with small cell lung cancer after second-line treatment failure. It has good therapeutic effect for patients with low ECOG score and without brain metastasis, and has tolerable adverse reactions and high safety.

Key words:Small cell lung carcinoma,Aged,Anlotinib,Efficacy analysis,Influencing factors

陶洁, 吴梅, 张琰. 安罗替尼治疗二线失败后老年小细胞肺癌患者的疗效及影响因素分析[J]. 国际肿瘤学杂志, 2022, 49(1): 39-44.

Tao Jie, Wu Mei, Zhang Yan. Efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure[J]. Journal of International Oncology, 2022, 49(1): 39-44.

图/表4

表1

56例老年小细胞肺癌患者临床病理特征与安罗替尼治疗疗效的关系[例(%)]"

临床病理特征	PR	SD			χ²值	P值	疾病控制	χ²值	P值
性别
男	4(10.3)	17(43.5)	18(46.2)	4(10.3)	0.028	0.867	21(53.8)	0.004	0.950
女	2(11.8)	7(41.2)	8(47.0)	2(11.8)			9(52.9)
年龄(岁)
>70	3(11.5)	11(42.3)	12(41.2)	3(11.5)	0.034	0.853	14(53.8)	0.001	0.969
≤70	3(10.0)	13(43.3)	14(46.7)	3(10.0)			16(53.3)
临床分期
局限期	2(9.5)	9(42.9)	10(47.6)	2(9.5)	0.050	0.823	11(52.4)	0.019	0.890
广泛期	4(11.4)	15(42.9)	16(45.7)	4(11.4)			19(54.3)
脑转移
有	1(3.1)	11(34.4)	20(62.5)	1(3.1)	4.496	0.034	12(37.5)	7.754	0.005
无	5(20.8)	13(54.2)	6(25.0)	5(20.8)			18(75.0)
吸烟状况
有	5(12.2)	18(43.9)	18(43.9)	5(12.2)	0.351	0.554	23(56.1)	0.393	0.531
无	1(6.7)	6(40.0)	8(53.3)	1(6.7)			7(46.7)
ECOG评分
0~1	5(21.7)	11(47.9)	7(30.4)	5(21.7)	4.959	0.026	16(69.6)	4.014	0.045
2~3	1(3.0)	13(39.4)	19(57.6)	1(3.0)			14(42.4)

表1

表2

影响56例使用安罗替尼治疗的老年小细胞肺癌患者PFS的单因素分析"

临床病理特征	例数	中位PFS(月)	χ²值	P值	临床病理特征	例数	中位PFS(月)	χ²值	P值
性别					脑转移
男	39	4.2	0.236	0.627		有	32	3.2	8.895	0.003
女	17	3.4				无	24	5.1
年龄(岁)						吸烟状况
>70	26	3.4	5.452	0.020		有	41	4.2	0.305	0.581
≤70	30	5.0				无	15	3.7
临床分期						ECOG评分
局限期	21	5.0	5.141	0.023		0~1分	23	5.0	5.923	0.015
广泛期	35	3.1				2~3分	33	2.9

表2

临床特征	β值	SE值	Wald值	HR值	95%CI	P值
年龄	0.475	0.503	0.893	1.609	0.600~4.312	0.345
临床分期	0.589	0.636	0.858	1.802	0.518~6.266	0.354
脑转移	-1.130	0.334	11.439	0.323	0.168~0.622	0.001
ECOG评分	0.925	0.308	8.996	2.522	1.378~4.615	0.003

表3

不良反应	Ⅰ~Ⅱ级	Ⅲ~Ⅳ级
手足综合征	21(37.5)	3(5.4)
咯血	4(7.1)	0(0)
乏力	12(21.4)	0(0)
高血压	9(16.1)	2(3.6)
肝功能损伤	5(8.9)	0(0)
蛋白尿	10(17.9)	0(0)
胃肠道反应	14(25.0)	0(0)

表4

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