阿帕替尼联合新辅助化疗对局部晚期结肠癌的临床疗效研究

doi:10.3877/cma.j.issn.1674-0793.2024.03.005

目的

探讨阿帕替尼联合新辅助化疗对局部晚期结肠癌治疗中的临床疗效和不良事件。

方法

设计前瞻性单臂试验，选择2019年1月至2020年12月联勤保障部队第九八〇医院收治的局部晚期大肠癌患者30例，给予阿帕替尼联合新辅助化疗后接受手术及辅助治疗，评估新辅助疗效、生存情况及治疗后不良事件。

结果

新辅助治疗后患者完全缓解（CR）、部分缓解（PR）、疾病稳定（SD）以及疾病进展（PD）的例数分别为0例（0）、17例（56.7%）、12例（40.0%）和1例（3.3%），客观缓解率为56.7%（17/30），疾病控制率为96.7%（29/30）。与治疗前相比，治疗后临床T分期、N分期和TNM分期均有所降低（均P<0.001）。6例（20.0%）实现了术后病理完全缓解（pCR），28例（93.3%）实现了R0切除。生存分析提示患者中位无进展生存期和总生存期分别为26.3个月和27.7个月。围手术期的不良事件多数为轻度（1~2级），少数为3级不良事件，未发现4级不良事件。

结论

新辅助治疗中阿帕替尼联合化疗在局部晚期大肠癌中显示出良好疗效。该方案严重不良事件发生率较低，是值得进一步探究的治疗策略。

关键词: 结肠肿瘤, 阿帕替尼, 血管内皮细胞生长因子受体, 新辅助治疗

Objective

To investigate the clinical efficacy and adverse events of Apatinib combined with neoadjuvant chemotherapy in the treatment of locally advanced colon cancer.

Methods

A prospective single-arm trial was designed. Thirty cases with locally advanced colon cancer admitted to the 980th Hospital of the Joint Logistics Support Force from January 2019 to December 2020 were selected. The patients received surgery and adjuvant therapy after administration of apatinib in combination with neoadjuvant chemotherapy, while neoadjuvant efficacy, survival, and adverse events after treatment were evaluated.

Results

The incidence of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) after neoadjuvant chemotherapy was 0 (0), 17 (56.7%), 12 (40.0%) and 1 (3.3%), respectively. The objective response rate was 56.7% and the disease control rate was 96.7%. Clinical T-stage, N-stage, and TNM-stage were reduced after treatment compared to the levels before treatment (all P<0.001). Pathological complete remission (pCR) was achieved in 6 (20.0%) patients and R0 resection was achieved in 28 (93.3%) patients. Survival analysis showed the median progression free survival (PFS) and overall survival (OS) were 26.3 months and 27.7 months, respectively. During perioperative treatment, most of the observed adverse events were mild (grade 1-2); only a few grade 3 adverse events were observed and no grade 4 adverse events were identified.

Conclusions

Neoadjuvant therapy with Apatinib in combination with chemotherapy has shown good efficacy in locally advanced colon cancer. This regimen has a low rate of serious adverse events and is a therapeutic strategy worthy of further investigation.

Key words: Colon neoplasms, Apatinib, Vascular endothelial growth factor receptor, Neoadjuvant therapy

表1 30例局部晚期结肠癌患者新辅助治疗前后的临床分期[例(%)]

临床分期	治疗前	治疗后	Z值	P值
T分期			3.755	<0.001
cT2	0(0)	7(23.3)
cT3	4(13.3)	9(30.0)
cT4	26(86.7)	14(46.7)
N分期			5.166	<0.001
cN0	0(0)	15(50.0)
cN1	12(40.0)	10(33.3)
cN2a	13(43.3)	4(13.3)
cN2b	5(16.7)	1(3.3)
TNM分期			3.800	<0.001
Ⅰ	0(0)	7(23.3)
Ⅱ	0(0)	12(40.0)
Ⅲ	30(100.0)	10(33.3)
Ⅳ	0(0)	1(3.3)

表1 30例局部晚期结肠癌患者新辅助治疗前后的临床分期[例(%)]

临床分期	治疗前	治疗后	Z值	P值
T分期			3.755	<0.001
cT2	0(0)	7(23.3)
cT3	4(13.3)	9(30.0)
cT4	26(86.7)	14(46.7)
N分期			5.166	<0.001
cN0	0(0)	15(50.0)
cN1	12(40.0)	10(33.3)
cN2a	13(43.3)	4(13.3)
cN2b	5(16.7)	1(3.3)
TNM分期			3.800	<0.001
Ⅰ	0(0)	7(23.3)
Ⅱ	0(0)	12(40.0)
Ⅲ	30(100.0)	10(33.3)
Ⅳ	0(0)	1(3.3)

图1 局部晚期结肠癌患者无进展生存期的Kaplan-Meier曲线

图2 局部晚期结肠癌患者总生存期的Kaplan-Meier曲线

表2 30例局部晚期结肠癌患者围手术期不良事件[例(%)]

不良事件	所有级别	1级	2级	3级	4级
血液学事件
白细胞减少	19(63.3)	4(13.3)	12(40.0)	3(10.0)	0(0)
血小板减少	16(53.3)	13(43.3)	2(6.7)	1(3.3)	0(0)
贫血	11(36.7)	5(16.7)	5(16.7)	1(3.3)	0(0)
非血液学事件
恶心	19(63.3)	10(33.3)	8(26.7)	1(3.3)	0(0)
疲劳	18(60.0)	13(43.3)	5(16.7)	0(0)	0(0)
转氨酶升高	13(43.3)	10(33.3)	3(10.0)	0(0)	0(0)
呕吐	10(33.3)	7(23.3)	2(6.7)	1(3.3)	0(0)
蛋白尿	11(36.7)	7(23.3)	3(10.0)	1(3.3)	0(0)
高血压	10(33.3)	8(26.7)	2(6.7)	0(0)	0(0)
腹泻	3(10.0)	2(6.7)	1(3.3)	0(0)	0(0)
手足综合征	2(6.7)	1(3.3)	1(3.3)	0(0)	0(0)

表2 30例局部晚期结肠癌患者围手术期不良事件[例(%)]

不良事件	所有级别	1级	2级	3级	4级
血液学事件
白细胞减少	19(63.3)	4(13.3)	12(40.0)	3(10.0)	0(0)
血小板减少	16(53.3)	13(43.3)	2(6.7)	1(3.3)	0(0)
贫血	11(36.7)	5(16.7)	5(16.7)	1(3.3)	0(0)
非血液学事件
恶心	19(63.3)	10(33.3)	8(26.7)	1(3.3)	0(0)
疲劳	18(60.0)	13(43.3)	5(16.7)	0(0)	0(0)
转氨酶升高	13(43.3)	10(33.3)	3(10.0)	0(0)	0(0)
呕吐	10(33.3)	7(23.3)	2(6.7)	1(3.3)	0(0)
蛋白尿	11(36.7)	7(23.3)	3(10.0)	1(3.3)	0(0)
高血压	10(33.3)	8(26.7)	2(6.7)	0(0)	0(0)
腹泻	3(10.0)	2(6.7)	1(3.3)	0(0)	0(0)
手足综合征	2(6.7)	1(3.3)	1(3.3)	0(0)	0(0)

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Apatinib combined with neoadjuvant chemotherapy in locally advanced colon cancer: A clinical efficacy study

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Apatinib combined with neoadjuvant chemotherapy in locally advanced colon cancer: A clinical efficacy study