Clinical Importance of Regimens in Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Macrovascular Invasion

Abstract

Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child-Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively (p < 0.05, p < 0.05). The complete response (29%) and objective response rate (76%) of New FP were significantly higher than those of LFP (p < 0.001, p < 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC.

Keywords: New FP; hepatic arterial infusion chemotherapy; hepatocellular carcinoma; low dose FP; macrovascular invasion; vascular invasion.

Figure 1

LFP and New FP for inpatient treatment regimens. (A) The LFP regimen. As an inpatient regimen, one course consisted of the daily administration of 10 mg of CDDP for 30 min from day 1 to day 5, followed by 250 mg of 5-FU continuously injected for 3 h from day 1 to day 5. Day 6 and 7 was the rest period. In principle, this weekly regimen was repeated 2 or 3 times as one cycle of LFP. (B) The New FP regimen. The fine-powder formulation of CDDP (DPP-H) was used in New FP regimen. The inpatient regimen comprised 50 mg of fine-powder DPP-H suspended in 5–10 mL of lipiodol, the amount of which was determined by the tumor volume. At day 1, the DPP-H-lipiodol suspension was injected from the implanted catheter under the angiography, followed by injection of 250 mg of 5-FU. Next, 1250 mg of 5-FU was continuously injected using an infusion balloon pump. This regimen was applied once a week during the first two weeks. LFP: Low dose CDDP plus 5-FU, CDDP: cisplatin, 5-FU: 5-fluorouracil.

Figure 2

The therapeutic outcomes of LFP and New FP. (A) Overall survival curve of the 150 patients treated with either LFP or New FP. The MST of 150 patients was 21.8 months. (B) Comparison of the survival curve between LFP and New FP group. The MST of LFP group was 16.1 months. The MST of New FP was 24.7 months. There was a significant difference between two groups (p < 0.05). (C) Comparison of Progression-free survival between LFP and New FP group. The PFS of LFP group was 5.4 months. The MST of New FP was 8.8 months. There was a significant difference between two groups (p < 0.05). (D) Comparison of the post-progression survival between LFP and New FP group. The PPS of LFP group was 6.8 months. The PPS of New FP was 11.5 months. There was no significant difference between two groups (p = 0.411). (E) The therapeutic response of LFP group. In LFP group, CR, PR, SD, and PD were 4, 43, 27, and 26%, respectively. (F)The therapeutic response of New FP group. In the New FP group, CR, PR, SD, and PD were 29, 47, 12, and 12%, respectively. (G) Comparison of the therapeutic response between LFP and New FP group. The ORR and DCR in LFP group were 47 and 74%, respectively. ORR and DCR in New FP group were 76% and 88%, respectively. There was a significant difference in ORR and DCR between two groups (p < 0.001 and p < 0.005, respectively.). LFP: Low dose CDDP plus 5-FU, MST: median survival time, CR: complete response, PR: partial response, SD: stable disease, PD: progressive disease, ORR: objective response rate, DCR: disease control rate. * p < 0.05, ** p < 0.01, *** p < 0.001, n.s.: not significant.

Figure 3

Detailed comparison of the survival curve of patients with HCC treated with either LFP or New FP. (A) Comparison of the survival curve of patients accompanied by PVTT into the portal trunk of the LFP and New FP groups. The MST of the LFP and New FP were 9.2 and 18.7 months, respectively. The MST of the New FP was significantly superior to that of LFP in patients with HCC accompanied with PVTT into portal trunk (p < 0.01). (B) Comparison of the survival curve of the responders and non-responders in the LFP group. The MST of the responders and non-responders in the LFP was 23.2 and 7.2 months, respectively (p < 0.001). (C) Comparison of the survival curve of the responder and non-responder in the New FP group. The MST of the responders and non-responders in New FP were 33.4 and 7.8 months, respectively (p < 0.001). (D) Comparison of the survival curve of the responders in the LFP and New FP treatment groups. The MST of the responders to LFP and New FP treatment was 23.2 and 33.4 months, respectively (n.s.). LFP: low dose CDDP plus 5-FU, MST: median survival time, PVTT: portal vein tumor thrombus, n.s.: not significant.