Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases

Abstract

Abstract:

ObjectiveTo explore the efficacy and influencing factors of irinotecan-loaded CalliSpheres drug-eluting bead-transcatheter arterial chemoembolization （DEBIRI-TACE） combined with regorafenib in the third-line or above treatment of unresectable colorectal cancer liver metastases.MethodsFrom June 2018 to June 2020, 53 patients with unresectable colorectal cancer liver metastases admitted to Linyi Cancer Hospital of Shandong Province who had failed at least second-line systemic chemotherapy were retrospectively analyzed. The patients were divided into observation group （24 cases） and control group （29 cases） according to different treatment regimes. The control group only received regorafenib monotherapy, and the observation group received regorafenib combined with DEBIRI-TACE. According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate （ORR） and disease control rate （DCR） were evaluated, and the progression-free survival （PFS） and overall survival （OS） were estimated by Kaplan-Meier method. The Cox proportional hazards model was used to analyze the OS influencing factors in the observation group. The treatment related adverse reactions were observed.ResultsAfter 2 months of treatment, the ORR of the observation group was 75.0% （18/24）, and the DCR was 91.7% （22/24）, both were higher than those of the control group [6.9% （2/29） and 51.7% （15/29） respectively], with statistically significant differences （χ²=25.92,P<0.001;χ²=9.94,P=0.002）. There were no statistically significant differences in the incidences of regorafenib-related adverse reactions such as hand-foot skin reaction [62.5% （15/24）vs.65.5% （19/29）,χ²=0.05,P=0.819], fatigue [41.7% （10/24）vs.44.8% （13/29）,χ²=0.05,P=0.817], hypertension [29.2% （7/24）vs.34.5% （10/29）,χ²=0.17,P=0.679], diarrhea [25.0% （6/24）vs.27.6% （8/29）,χ²=0.04,P=0.832], hoarseness [16.7% （4/24）vs.17.2% （5/29）,χ²=0.01,P=0.956] and proteinuria [8.3% （2/24）vs.10.3% （3/29）,χ²=0.06,P=0.803] between the two groups. The main adverse reactions related to DEBIRI-TACE in the observation group were fever, pain, nausea and vomiting,etc., which were relieved after symptomatic treatment. No serious complications such as ectopic embolism of CalliSpheres drug eluting bead occurred. By the end of the follow-up,among the 24 patients in the observation group, the median OS of patients with simultaneous liver metastases was 12 months, and that of patients with metachronous liver metastases was 22 months, with a statistically significant difference （χ²=4.29,P=0.026）. The median OS of patients with 3-5 liver metastases was 21 months, and that of patients with more than 5 liver metastases was 14 months, with a statistically significant difference （χ²=3.35,P=0.040）. The median OS of Child-Pugh grade A patients was 22 months, and that of Child-Pugh grade B patients was 13 months, with a statistically significant difference （χ²=4.22,P=0.027）. The median OS was 16 months in patients with extrahepatic metastases and 23 months in patients without extrahepatic metastases, with a statistically significant difference （χ²=7.68,P=0.013）. Cox proportional hazards model analysis showed that simultaneous liver metastases （HR=1.59, 95%CI： 1.02-2.47,P=0.031） and extrahepatic metastases （HR=1.61, 95%CI： 1.29-2.01,P=0.020） were independent risk factors influencing OS of patients in the observation group. The median PFS of the observation group was 9 months, and that of the control group was 5 months, with a statistically significant difference （χ²=7.78,P=0.005）. The median OS of the observation group was 17 months, and that of the control group was 11 months, with a statistically significant difference （χ²=16.81,P<0.001）.ConclusionDEBIRI-TACE combined with regorafenib is effective in the third-line or above treatment of unresectable colorectal cancer liver metastases, with tolerable adverse reactions. It is a safe and feasible treatment method. The prognosis of patients with simultaneous liver metastases or extrahepatic metastases is worse.

Key words:Colorectal neoplasms,Treatment outcome,Transcatheter arterial chemoembolization,Liver metastases,Regorafenib

Liu Song, Yu Guangji, Wang Qingdong. Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases[J]. Journal of International Oncology, 2022, 49(7): 400-407.

Figures/Tables7

临床特征	观察组（n=24）	对照组（n=29）	t/χ²值	P值
年龄（岁）	58.6±6.9	59.2±7.1	0.31	0.379
性别
男	15（62.5）	17（58.6）	0.08	0.773
女	9（37.5）	12（41.4）	0.08	0.773
肝转移类型
同时性	6（25.0）	7（24.1）	0.01	0.942
异时性	18（75.0）	22（75.9）	0.01	0.942
肝转移癌数目（个）
3~5	7（29.2）	9（31.0）	0.02	0.883
>5	17（70.8）	20（69.0）	0.02	0.883
肿瘤大小（cm）
<5	11（45.8）	13（44.8）	0.01	0.942
≥5	13（54.2）	16（55.2）	0.01	0.942
肝外转移
是	13（54.2）	15（51.7）	0.03	0.859
否	11（45.8）	14（48.3）	0.03	0.859
肝功能分级
Child-Pugh A	21（87.5）	25（86.2）	0.02	0.889
Child-Pugh B	3（12.5）	4（13.8）	0.02	0.889
ECOG评分（分）
0	18（75.0）	21（72.4）
1	5（20.8）	6（20.7）	0.19	0.192
2	1（4.2）	2（6.9）
原发肿瘤位置
直肠	10（41.7）	12（41.4）
左结肠	6（25.0）	7（24.1）	0.01	0.955
右结肠	8（33.3）	10（34.5）

不良反应	1级	2级
发热	13（54.2）	6（25.0）
疼痛	11（45.8）	3（12.5）
恶心呕吐	8（33.3）	3（12.5）
肝功能损害	6（25.0）	1（4.2）
骨髓抑制	2（8.3）	1（4.2）
迟发型腹泻	1（4.2）	0（0）

不良反应	观察组（n=24）			对照组（n=29）			χ²值	P值
不良反应	1~2级（例）	3~4级（例）	发生率（%）	1~2级（例）	3~4级（例）	发生率（%）	χ²值	P值
手足皮肤反应	13	2	62.5	16	3	65.5	0.05	0.819
乏力	8	2	41.7	12	1	44.8	0.05	0.817
高血压	7	0	29.2	10	0	34.5	0.17	0.679
腹泻	5	1	25.0	6	2	27.6	0.04	0.832
声音嘶哑	4	0	16.7	5	0	17.2	0.01	0.956
蛋白尿	2	0	8.3	3	0	10.3	0.06	0.803

影响因素	例数	中位OS（月）	χ²值	P值
年龄（岁）
<60	14	16	1.57	0.163
≥60	10	19	1.57	0.163
性别
男	15	18	0.39	0.768
女	9	15	0.39	0.768
肝转移类型
同时性	6	12	4.29	0.026
异时性	18	22	4.29	0.026
肝转移癌数目（个）
3~5	7	21	3.35	0.040
>5	17	14	3.35	0.040
肿瘤大小（cm）
<5	11	20	1.38	0.194
≥5	13	18	1.38	0.194
肝外转移
是	13	16	7.68	0.013
否	11	23	7.68	0.013
肝功能分级
Child-Pugh A	21	22	4.22	0.027
Child-Pugh B	3	13	4.22	0.027
ECOG评分（分）
0	18	20	1.03	0.516
1	5	15
2	1	14
原发肿瘤位置
直肠	10	23	1.00	0.691
左结肠	6	19
右结肠	8	17

因素	HR值	95%CI	P值
肝转移类型（异时性/同时性）	1.59	1.02~2.47	0.031
肝转移癌数目（3~5个/>5个）	1.21	0.93~1.56	0.174
肝功能分级（Child-Pugh A/Child-Pugh B）	0.96	0.82~1.12	0.865
肝外转移（否/是）	1.61	1.29~2.01	0.020

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