Clinical Application And Safety Analysis Of Continuous Hepatic Arterial Infusion In Colorectal Cancer Liver Metastases

BACKGROUND AND PURPOSE:Colorectal cancer(CRC)is the third most prevalent malignancy worldwide,and the liver is the most common site of metastasis,about 2/3 of CRC patients die due to liver metastasis.Treatment of liver metastases is aggressive throughout the course of CRC treatment.In addition to surgery and systemic therapy,hepatic arterial infusion chemotherapy(HAIC)is also widely used in patients with colorectal cancer liver metastases(CRCLM)because of its reproducibility,minimally invasive nature and high local control rate.It is widely used in patients with CRCLM.However,there is no standard drug regimen for HAIC,and previous clinical trials mainly referred to systemic therapy.It has been found that oxaliplatin and 5-Fu(FOLFOX)remain effective in HAIC in patients who have progressed after previous systemic chemotherapy regimens based on FOLFOX,and that the combination of bevacizumab(Bev)improves the prognosis of patients.5-Fu is commonly used in HAIC,because of its infusion time of 24-44 hours,the prolonged bed rest of patients leads to an increased risk of thrombotic events and affects the quality of life of patients.Raltitrexed as an alternative to 5-Fu can significantly reduce the perfusion time.The purpose of this study:(1)To investigate the safety of FOLFOX in combination with Bev by HAIC and its survival benefit.(2)To compare the efficacy and safety of FOLFOX and oxaliplatin in combination with raltitrexed(TOMOX)by HAIC.MATERIALS AND METHODS:(1)The retrospective study reviewed the electronic medical records of consecutive patients with CRCLM from 2006 to 2016,who failed previous first-or second-line FOLFXO-containing regimens and received treatment with HAIC FOLFOX ± bevacizumab.(2)Design a prospective randomized controlled trial for CRCLM who progressed after previous first-or second-line systemic therapy,or who could not tolerate systemic therapy.The patients were randomly assigned(1:1)to receive HAIC of TOMOX or FOLFOX.Drug doses:oxaliplatin 85 mg/m2,pumped for 4 hours;5-Fu 2000 mg/m2,pumped for 44 hours;formyltetrahydrofolate 200 mg/m2,pumped for 2 hours via peripheral Ⅳ;Bev 5 mg/kg,pumped for 4 hours;and raltitrexed 3 mg/m2,pumped for 1 hour.HAIC was administered every 4 weeks until disease progression or intolerance.The Common Terminology Criteria for Adverse Events(CTCAE 5.0)was applied to evaluate the adverse reactions.RESULTS:(1)A total of 100 patients were included in the retrospective part of the study,41 in the FOLFOX+Bev group and 59 in the FOLFOX group.Median overall survival(mOS)was 14.6 months and 12.7 months in the FOLFOX+Bev and FOLFOX groups,respectively(p=0.013).Grade 3-4 transaminase elevations were more common in the FOLFOX+Bev group than in the FOLFOX group(37%versus 19%,p=0.044).(2)A total of 113 patients were enrolled in the prospective study,52 patients in the FOLFOX group and 61 patients in the TOMOX group.mOS was 17.6 months and 13.1 months(p=0.178)and mPFS was 5.8 months and 4.6 months(p=0.840)in the FOLFOX and TOMOX groups,respectively.The incidence of adverse reactions was similar in both groups.CONCLUSION:CRCLM who failed previous first-or second-line FOLFOX-containing therapy remained effective with HAIC FOLFOX.The combination of Bev significantly improved survival but increased the incidence of elevated transaminases.FOLFOX was slightly superior to TOMOX,but did not reach statistical difference.TOMOX significantly shortened the duration of HAIC.