Neutrophil/lymphocyte ratio as a prognostic indicator of hepatic arterial infusion chemotherapy with arterial cisplatin plus continuous 5-fluorouracil
Corresponding Author
Kazuto Tajiri
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Correspondence: Dr Kazuto Tajiri, The Third Department of Internal Medicine, Toyama University Hospital, 2630 Sugitani, Toyama 930-0194, Japan. Email: [email protected]Search for more papers by this authorKengo Kawai
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorMasami Minemura
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorSatoshi Yasumura
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorAyumu Hosokawa
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorHideto Kawabe
Department of Radiology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorGakuto Tomizawa
Department of Radiology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorToshiro Sugiyama
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorCorresponding Author
Kazuto Tajiri
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Correspondence: Dr Kazuto Tajiri, The Third Department of Internal Medicine, Toyama University Hospital, 2630 Sugitani, Toyama 930-0194, Japan. Email: [email protected]Search for more papers by this authorKengo Kawai
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorMasami Minemura
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorSatoshi Yasumura
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorAyumu Hosokawa
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorHideto Kawabe
Department of Radiology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorGakuto Tomizawa
Department of Radiology, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorToshiro Sugiyama
The Third Department of Internal Medicine, Toyama University Hospital, Toyama, Japan
Search for more papers by this authorAbstract
Aim
Hepatic arterial infusion (HAIC) therapy may be a therapeutic option for advanced hepatocellular carcinoma (HCC) in addition to administration of sorafenib, which is the only currently established standard regimen for this disease. Survival benefit of HAIC has been reported in patients positive for antitumor response. Therefore, the prediction of antitumor response is important in decision-making for HAIC treatment.
Methods
Twenty-six consecutive patients with advanced HCC treated by HAIC using arterial cisplatin plus continuous 5-fluorouracil were retrospectively analyzed in this study. Neutrophil/lymphocyte ratio (NLR) was assessed to determine its effectiveness as a prognostic indicator of HAIC.
Results
The median time to progression and overall survival time (OS) were 5.0 and 17.0 months, respectively. The overall response rate (RR) among the 26 patients was 42.3%, and RR was independent of liver function. Interestingly, RR was significantly lower in patients with NLR of 4 or more (odds ratio, 0.49; P = 0.04). When we investigated factors that influenced OS, treatment effect and NLR of less than 4 were associated with prolonged OS. No serious adverse events were found in treatment with HAIC.
Conclusion
HAIC is a candidate for treatment of advanced HCC, and NLR may be a useful prognostic indicator for suitability of HAIC.
References
- 1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–2917.
- 2 El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118–1127.
- 3 Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378–390.
- 4 Cheng AL, Kang YK, Chen Z 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.
- 5 Kudo M. Treatment of advanced hepatocellular carcinoma with emphasis on hepatic arterial infusion chemotherapy and molecular targeted therapy. Liver Cancer 2012; 1: 62–70.
- 6 Nouso K, Miyahara K, Uchida D et al. Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan. Br J Cancer 2013; 109: 1904–1907.
- 7 Shao YY, Huang CC, Liang PC, Lin ZZ. Hepatic arterial infusion of chemotherapy for advanced hepatocellular carcinoma. Asia Pac J Clin Oncol 2010; 6: 80–88.
- 8 Nagano H. Treatment of advanced hepatocellular carcinoma: intraarterial infusion chemotherapy combined with interferon. Oncology 2010; 78 (Suppl 1): 142–147.
- 9 Ando E, Tanaka M, Yamashita F et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer 2002; 95: 588–595.
- 10 Lai YC, Shih CY, Jeng CM et al. Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 2003; 9: 2666–2670.
- 11 Kim BK, Park JY, Choi HJ et al. Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 2011; 137: 659–667.
- 12 Eun JR, Lee HJ, Moon HJ, Kim TN, Kim JW, Chang JC. Hepatic arterial infusion chemotherapy using high-dose 5-fluorouracil and cisplatin with or without interferon-alpha for the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis. Scand J Gastroenterol 2009; 44: 1477–1486.
- 13 Lim TY, Cheong JY, Cho SW 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.
- 14 Ueshima K, Kudo M, Takita M et al. Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma. Oncology 2012; 78 (Suppl 1): 148–153.
- 15 Toyoda H, Nakano S, Kumada T et al. The efficacy of continuous local arterial infusion of 5-fluorouracil and cisplatin through an implanted reservoir for severe advanced hepatocellular carcinoma. Oncology 1995; 52: 295–299.
- 16 Okuda K, Tanaka M, Shibata J et al. Hepatic arterial infusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma after surgical treatment. Oncol Rep 1999; 6: 587–591.
- 17 Nagamatsu H, Hiraki M, Mizukami N et al. Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis. Aliment Pharmacol Ther 2010; 32: 543–550.
- 18 Scanlon KJ, Newman EM, Lu Y, Priest DG. Biochemical basis for cisplatin and 5-fluorouracil synergism in human ovarian carcinoma cells. Proc Natl Acad Sci U S A 1986; 83: 8923–8925.
- 19 Shirasaka T, Shimamoto Y, Ohshimo H, Saito H, Fukushima M. Metabolic basis of the synergistic antitumor activities of 5-fluorouracil and cisplatin in rodent tumor models in vivo. Cancer Chemother Pharmacol 1993; 32: 167–172.
- 20 Bruix J, Sherman M, Llovet JM et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421–430.
- 21 Zahorec R. Ratio of neutrophil to lymphocyte counts – rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001; 102: 5–14.
- 22 Xiao WK, Chen D, Li SQ, Fu SJ, Peng BG, Liang LJ. Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis. BMC Cancer 2014; 14: 117.
- 23 Shindoh N, Ozaki Y, Kyogoku S, Yamana D, Sumi Y, Katayama H. Stabilization of a percutaneously implanted port catheter system for hepatic artery chemotherapy infusion. Cardiovasc Intervent Radiol 1999; 22: 344–347.
- 24 Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res 1982; 42: 4413–4420.
- 25 Yoshikawa M, Ono N, Yodono H, Ichida T, Nakamura H. Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 2008; 38: 474–483.
- 26 Ikeda M, Okusaka T, Furuse J et al. A multi-institutional phase II trial of hepatic arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Cancer Chemother Pharmacol 2013; 72: 463–470.
- 27 Kim HY, Kim JD, Bae SH et al. A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable, advanced hepatocellular carcinoma. Korean J Hepatol 2010; 16: 355–361.
- 28 Kirikoshi H, Yoneda M, Mawatari H et al. Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization? World J Gastroenterol 2012; 18: 1933–1939.
- 29 Miyaki D, Aikata H, Honda Y et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma according to Child-Pugh classification. J Gastroenterol Hepatol 2012; 27: 1850–1857.
- 30 Niizeki T, Sumie S, Torimura T et al. Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy. J Gastroenterol 2012; 47: 686–695.
- 31 Oh MJ, Lee HJ, Lee SH. Efficacy and safety of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma as first-line therapy. Clin Mol Hepatol 2013; 19: 288–299.
- 32 Shao YY, Liang PC, Wu YM et al. A pilot study of hepatic arterial infusion of chemotherapy for patients with advanced hepatocellular carcinoma who have failed anti-angiogenic therapy. Liver Int 2013; 33: 1413–1419.
- 33 Park JY, Ahn SH, Yoon YJ et al. Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma. Cancer 2007; 110: 129–137.
- 34 Woo HY, Bae SH, Park JY 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.
- 35 Yamasaki T, Kimura T, Kurokawa F et al. Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. J Gastroenterol 2005; 40: 70–78.
- 36 Zaitsu J, Yamasaki T, Saeki I et al. Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma. Hepatol Res 2014; 44: 481–490.
- 37 Mano Y, Shirabe K, Yamashita Y et al. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg 2013; 258: 301–305.
- 38 Harimoto N, Shirabe K, Nakagawara H et al. Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio. Transplantation 2013; 96: 1008–1012.
- 39 Huang ZL, Luo J, Chen MS, Li JQ, Shi M. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization. J Vasc Interv Radiol 2011; 22: 702–709.
- 40 Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140: 883–899.
- 41 Svennevig JL, Lunde OC, Holter J, Bjorgsvik D. Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 1984; 49: 375–377.
- 42 Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 2011; 331: 1565–1570.
- 43 Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307: 58–62.
- 44 Kerbel RS. Antiangiogenic therapy: a universal chemosensitization strategy for cancer? Science 2006; 312: 1171–1175.
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