Efficacy and influencing factors of DEBIRI-TACE combined with regorafenib in the third-line or above treatment of colorectal cancer liver metastases / 国际肿瘤学杂志

ABSTRACT

Objective:To 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.Methods:From 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.Results:After 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) . Conclusion:DEBIRI-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.