J Liver Cancer.  2019 Mar;19(1):38-45. 10.17998/jlc.19.1.38.

High-dose versus Low-dose 5-Fluorouracil and Cisplatin Based Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma

Affiliations
  • 1Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. portalvein@naver.com
  • 2Department of General Surgery, Chonnam National University Medical School, Gwangju, Korea.

Abstract

BACKGROUND/AIMS
Hepatic arterial infusion chemotherapy (HAIC) has been reported as an effective treatment for advanced hepatocellular carcinoma. The aim of this study is to compare the effect and safety between a high-dose regimen (750 mg/m2 5-fluorouracil [FU] and 25 mg/m2 cisplatin on day 1-4) and a low-dose regimen (500 mg/m2 5-FU on day 1-3 with 60 mg/m2 cisplatin on day 2).
METHODS
A total of 48 patients undergoing HAIC were retrospectively analyzed. Thirty-two patients were treated with the high-dose and 16 patients with the low-dose regimen.
RESULTS
Complete response (CR), partial response (PR), stable disease (SD), and progressive disease were noted in one (3.1%), 15 (46.9%), three (9.4%), and 13 patients (40.6%) in the highdose group, and 0 (0%), one (6.3%), eight (50%), and seven patients (43.8%) in the low-dose group (P=0.002). The disease control rate (CR, PR, and SD) did not differ between groups (59.4% vs. 56.3%, P=1.000), but the objective response rate (CR and PR) was significantly higher in the high-dose group (50.0% vs. 6.3%, P=0.003). The median progression free survival did not differ between groups (4.0 vs. 6.0, P=0.734), but overall survival was significantly longer in the high-dose group (not reached vs. 16.0, P=0.028). Fourteen (43.8%) patients in the high-dose group and two patients (12.5%) in the low-dose group experienced grade 3-4 toxicities (P=0.050).
CONCLUSIONS
High dose HAIC may achieve better tumor response and may improve overall survival compared to a low-dose regimen. However, the high-dose regimen should be administered cautiously because of the higher incidence of adverse events.

Keyword

Hepatocellular carcinoma; Chemotherapy, cancer, regional perfusion; Administration, metronomic

MeSH Terms

Administration, Metronomic
Carcinoma, Hepatocellular*
Chemotherapy, Cancer, Regional Perfusion
Cisplatin*
Disease-Free Survival
Drug Therapy*
Fluorouracil*
Humans
Incidence
Retrospective Studies
Cisplatin
Fluorouracil

Figure

  • Figure 1. Comparison of (A) progression-free survival and (B) overall survival between high-dose and low-dose regimen.


Reference

1. Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol. 2006; 12:7561–7567.
2. Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso MC, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999; 29:62–67.
3. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009; 10:25–34.
4. Jun CH, Yoon JH, Cho E, Shin SS, Cho SB, Kim HJ, et al. Barcelona clinic liver cancer-stage C hepatocellular carcinoma: a novel approach to subclassification and treatment. Medicine (Baltimore). 2017; 96:e6745.
5. Bartkowski R, Berger MR, Aguiar JL, Henne TH, Dörsam J, Geelhaar GH, et al. Experiments on the efficacy and toxicity of locoregional chemotherapy of liver tumors with 5-fluoro-2’-deoxyuridine (FUDR) and 5-fluorouracil (5-FU) in an animal model. J Cancer Res Clin Oncol. 1986; 111:42–46.
6. Kuan HY, Smith DE, Ensmiger WD, Knol JA, DeRemer SJ, Yang Z, et al. Regional pharmacokinetics of 5-bromo-2’-deoxyuridine and 5-fluorouracil in dogs: hepatic arterial versus portal venous infusions. Cancer Res. 1996; 56:4724–4727.
7. Woo HY, Bae SH, Park JY, Han KH, Chun HJ, Choi BG, et al. A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2010; 65:373–382.
8. Song DS, Song MJ, Bae SH, Chung WJ, Jang JY, Kim YS, et al. A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol. 2015; 50:445–454.
9. Kondo M, Morimoto M, Ishii T, Nozaki A, Fukuda H, Numata K, et al. Hepatic arterial infusion chemotherapy with cisplatin and sorafenib in hepatocellular carcinoma patients unresponsive to transarterial chemoembolization: a propensity score-based weighting. J Dig Dis. 2015; 16:143–151.
10. Baek YH, Kim KT, Lee SW, Jeong JS, Park BH, Nam KJ, et al. Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma. World J Gastroenterol. 2012; 18:3426–3434.
11. Song DS, Bae SH, Song MJ, Lee SW, Kim HY, Lee YJ, et al. Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol. 2013; 19:4679–4688.
12. Lim TY, Cheong JY, Cho SW, Sim SJ, Kim JS, Choi SJ, et al. Effect of low dose 5-fluorouracil and cisplatin intra-arterial infusion chemotherapy in advanced hepatocellular carcinoma with decompensated cirrhosis. Korean J Hepatol. 2006; 12:65–73.
13. Yamashita T. Current status of hepatocellular carcinoma treatment in Japan: hepatic arterial infusion chemotherapy. Clin Drug Investig. 2012; 32 Suppl 2:15–23.
14. Oh MJ, Lee HJ, Lee SH. Efficacy and safety of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma as firstline therapy. Clin Mol Hepatol. 2013; 19:288–299.
15. Song MJ, Bae SH, Chun HJ, Choi JY, Yoon SK, Park JY, et al. A randomized study of cisplatin and 5-FU hepatic arterial infusion chemotherapy with or without adriamycin for advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2015; 75:739–746.
16. Thomas MB. Systemic therapy for hepatocellular carcinoma. Cancer J. 2008; 14:123–127.
17. Miyaki D, Kawaoka T, Aikata H, Kan H, Fujino H, Fukuhara T, et al. Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of response evaluation criteria in solid tumors and tumor markers. J Gastroenterol Hepatol. 2015; 30:726–732.
18. Lin CC, Hung CF, Chen WT, Lin SM. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein thrombosis: impact of early response to 4 weeks of treatment. Liver Cancer. 2015; 4:228–240.
19. Kudo M, Ueshima K, Yokosuka O, Ogasawara S, Obi S, Izumi N, et al. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol. 2018; 3:424–432.
20. Kodama K, Kawaoka T, Aikata H, Uchikawa S, Nishida Y, Inagaki Y, et al. Comparison of outcome of hepatic arterial infusion chemotherapy combined with radiotherapy and sorafenib for advanced hepatocellular carcinoma patients with major portal vein tumor thrombosis. Oncology. 2018; 94:215–222.
Full Text Links
  • JLC
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr