Transarterial Chemoembolization Followed by Hepatic Arterial Infusion Chemotherapy Combined a Tyrosine Kinase Inhibitor for Treatment of Large Hepatocellular Carcinoma

Abstract

Objective: Evaluate the efficacy and safety of transarterial chemoembolization (TACE) sequential with hepatic arterial infusion chemotherapy (HAIC) and a tyrosine kinase inhibitor (TKI) for unresectable large hepatocellular carcinoma (HCC). Methods: Patients with HCC size > 70 mm were included. They received 1-3 cycles of TACE and sequential HAIC every 3-6 weeks for 2-6 cycles, with each cycle given over a period of 48 hours (oxaliplatin plus fluorouracil/leucovorin). Patients also received sorafenib or lenvatinib beginning at the first TACE cycle and continuing until disease progression. Objective response rate (ORR) at 3 months was the primary endpoint. Progression-free survival (PFS) and safety were the secondary endpoints. Results: From January 2020 to December 2020, 41 patients were included, who were divided into the drug-eluting bead TACE (DEB-TACE) group (n=13) and conventional TACE (cTACE) group (n=28). The overall ORR was 56.1% (23/41) using mRECIST criteria and 34.1% (14/41) using RECIST1.1 criteria. The median PFS of the cohort was 8 months. The ORR of the DEB-TACE group was 76.9% (10/13) vs. 46.4% (13/28) for the cTACE group (p = 0.06). The median PFS of the DEB-TACE group was 12 months, and 6 months in the cTACE group (p = 0.09). Conversion hepatectomy was performed in 2 patients in the DEB-TACE group (15.4%), and in 3 patients in the cTACE group (10.7%). ALT/AST elevated, hypertension, nausea, and vomiting were the common treatment related adverse events. There was no treatment related death. method: Patients with HCC size > 70 mm were included. They received 1-3 cycle of TACE and sequential HAIC every 3-6 weeks for 2-6 cycles, with each cycle given over a period of 48 hours (oxaliplatin plus fluorouracil/leucovorin). Patients also received sorafenib or Lenvatinib beginning at the first TACE cycle and continuing until disease progression. Objective response rate (ORR) in 3 month was the primary endpoint. Progression-free survival (PFS) and safety were the secondary endpoints. Conclusion: TACE sequential with HAIC combined with a TKI is a well-tolerated and promising triple-therapy for large, unresectable HCC.

Comparative study on the efficacy and safety of transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for large unresectable hepatocellular carcinoma

“…The ORR and DCR in the TACE-HAIC group were higher than those in the HAIC group (65.6% vs. 53.7% and 90.6% vs. 78.0%, respectively), although the differences were not statistically significant. This may be explained as follows: TACE promotes tumor cell necrosis, intertissue ion transport, and interstitial hypertension changes, which together contribute to the distribution of chemotherapeutic drugs ( 16 , 17 ). TACE can block the tumor’s main blood vessels, whereas HAIC is more conducive to the control of tumors with deficient blood supply ( 17 ).…”

“…This may be explained as follows: TACE promotes tumor cell necrosis, intertissue ion transport, and interstitial hypertension changes, which together contribute to the distribution of chemotherapeutic drugs ( 16 , 17 ). TACE can block the tumor’s main blood vessels, whereas HAIC is more conducive to the control of tumors with deficient blood supply ( 17 ). The combination of TACE and HAIC integrates the advantages of both to achieve better tumor control.…”

“…objective response rate (ORR) was calculated as CR + PR and disease control rate (DCR) was computed as CR + PR + SD. The Common Adverse Event Evaluation Criteria (CTCAE) version 5.0 ( 17 ) was adopted to assess treatment-related adverse reactions.…”

Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization

“…Combination therapy for TACE-refractory HCC has been explored ( 18 ). For example, several studies have shown that the combination of HAIC plus TKI resulted in better survival outcomes compared to TKI or HAIC monotherapy ( 32 , 35 , 36 ). The OS reported in our study was 9.0 months, which was lower compared to previous clinical trials ( 37 , 38 ).…”