Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Tajima,Hidehiro; Ohta,Tetsuo; Kitagawa,Hirohisa; Sakai,Seisho; Makino,Isamu; Hayashi,Hironori; Oyama,Katsunobu; Nakagawara,Hisatoshi; Fujita,Hideto; Onishi,Ichiro; Takamura,Hiroyuki; Ninomiya,Itasu; Fushida,Sachio; Tani,Takashi; Fujimura,Takashi; Koda,Wataru; Minami,Tetsuya; Ryu,Yasuji; Sanada,Junichiro; Gabata,Toshifumi; Matsui,Osamu

doi:10.3892/etm.2011.190

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Authors:
- Hidehiro Tajima
- Tetsuo Ohta
- Hirohisa Kitagawa
- Seisho Sakai
- Isamu Makino
- Hironori Hayashi
- Katsunobu Oyama
- Hisatoshi Nakagawara
- Hideto Fujita
- Ichiro Onishi
- Hiroyuki Takamura
- Itasu Ninomiya
- Sachio Fushida
- Takashi Tani
- Takashi Fujimura
- Wataru Koda
- Tetsuya Minami
- Yasuji Ryu
- Junichiro Sanada
- Toshifumi Gabata
- Osamu Matsui
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Affiliations: Department of Gastroenterologic Surgery, Graduate School of Medicine Science, Kanazawa University, Kanazawa 920-8641, Japan, Department of Radiology, Graduate School of Medicine Science, Kanazawa University, Kanazawa 920-8641, Japan
Published online on: January 12, 2011 https://doi.org/10.3892/etm.2011.190
Pages: 265-269

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Abstract

Hepatic metastasis is a common cause of treatment failure after curative resection of pancreatic cancer. We report a pilot study of hepatic arterial infusion (HAI) chemotherapy with gemcitabine and 5-fluorouracil (5-FU) for postoperative liver metastases from pancreatic cancer. Five patients who had undergone curative resection of liver metastases from pancreatic cancer received HAI of gemcitabine and 5-FU between October 2008 and September 2010 at Kanazawa University Hospital. Gemcitabine at a dose of 800 mg was infused over 30 min via a bedside pump. After gemcitabine administration, 250 mg of 5-FU was infused continuously over 24 h on days 1-5, comprising one cycle of therapy. These treatment cycles were continued biweekly. In the evaluation according to RECIST criteria, a partial response was obtained in 2 of the 5 cases, with stable disease being achieved in the remaining 3 cases (response rate, 100%). In 4 of the 5 cases, a decrease in serum tumor marker CA19-9 was observed after 10 HAI treatment cycles. The median time to treatment failure was 10 months (range 3-17). As to adverse events, leukocytopenia was grade 3 in 1 of 4 affected cases and all 5 were anemic, although 4 of the 5 cases had anemia prior to HAI therapy. Grade 2 thrombocytopenia was observed in 2 cases. No non-hematologic events, such as nausea, diarrhea, liver injury and neuropathy, occurred. There were no life-threatening toxicities, but 4 cases (80%) developed catheter complications, and the HAI catheter and subcutaneous implantable port system had to be removed. HAI delivers high doses of chemotherapeutic agents directly into tumor vessels, producing increased regional levels with greater efficacy and a lower incidence/severity of systemic side effects. In conclusion, HAI chemotherapy is useful and safe for the treatment of malignancies confined to the liver.

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1.	International Agency for Research on Cancer, World Health Organization. Globocan 2008. World Health Organization Web site. http://globocan.iarc.fr/uri. Accessed October 1, 2010.
2.	Ishii H, Furuse J, Boku N, et al: Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506. Jpn J Clin Oncol. 40:573–579. 2010. View Article : Google Scholar : PubMed/NCBI
3.	Evans DB, Abbruzzese JL and Willett CG: Cancer of the pancreas. Cancer: Priciples and Practice of Oncology. 6th edition. De Vita, Hellman S and Rosenberg SA: Lippincott, Williams and Wilkins; Philadelphia: pp. 1126–1161. 2001
4.	Oettle H, Post S, Neuhaus P, et al: Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 297:267–277. 2007. View Article : Google Scholar
5.	Aloia TE, Lee JE, Vauthey JN, et al: Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant chemotherapy? J Am Coll Surg. 204:347–355. 2007. View Article : Google Scholar : PubMed/NCBI
6.	Sandy H, Bruckner H, Cooperman A, Paradiso J and Kiefer L: Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial Cancer. 89:314–327. 2000.
7.	Ensminger WD, Rosowsky A and Raso V: A clinical pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2-deoxyuridine and 5-fluorourcil. Cancer Res. 38:3784–3792. 1978.PubMed/NCBI
8.	Vogl TJ, Schwarz W, Eichler K, et al: Hepatic intraarterial chemotherapy with gemcitabine in patients witn unresectable cholangiocarcinoma and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy. J Cancer Res Clin Oncol. 132:745–755. 2006. View Article : Google Scholar
9.	Tse AN, Wu N, Patel D, Haviland D and Kemeny N: A phase I study of gemcitabine given via intrahepatic pump for primary or metastatic hepatic malignancies. Cancer Chemother Pharmacol. 64:935–944. 2009. View Article : Google Scholar : PubMed/NCBI
10.	Van Riel JM, Peters GJ, Mammatas LH, et al: A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion. Eur J Cancer. 45:2519–2527. 2009.PubMed/NCBI
11.	Tajima H, Ohta T, Kitagawa H, et al: Hepatic arterial infusion chemotherapy for post-operative liver metastases from pancreatic cancer in a patient with leukocytopenia: a case report. Exp Therap Med. 1:987–990. 2010.PubMed/NCBI
12.	Urata K, Kawasaki S, Matsunami T, et al: Calculation of child and adult standard liver volume for liver transplantation. Hepatology. 21:1317–1321. 1995.PubMed/NCBI
13.	Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar
14.	Nagakawa T, Nagamori M, Futakami F, et al: Result of extensive surgery for pancreatic carcinoma. Cancer. 77:640–645. 1996. View Article : Google Scholar : PubMed/NCBI
15.	Noto M, Miwa K, Kitagawa H, et al: Pancreas head carcinoma. Frequency of invasion to soft tissue adherent to the superior mesenteric artery. Am J Surg Pathol. 29:1056–1061. 2005.PubMed/NCBI
16.	Spitz FR, Abbruzzese JL, Lee JE, et al: Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 15:928–937. 1997.PubMed/NCBI
17.	Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L and Benson AB: Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 16:317–323. 1998.
18.	Palmer DH, Stocken DD, Hewitt H, et al: A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemicitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 14:2088–2096. 2007. View Article : Google Scholar
19.	Golcher H, Brunner T, Grabenbauer G, et al: Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. Eur J Surg Oncol. 34:756–764. 2008. View Article : Google Scholar : PubMed/NCBI
20.	Turrini O, Viret F, Zabotto LM, et al: Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in patients with resectable pancreatic head adenocarcinoma: a ten-year single institution experience. Oncology. 76:413–419. 2009.
21.	Takai S, Satoi S, Yanagimoto H, et al: Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas. 36:26–32. 2008. View Article : Google Scholar : PubMed/NCBI
22.	Satoi S, Yanaagimoto H, Toyokawa H, et al: Surgical results after prepoerative chemoradiation therapy for patients with pancreatic cancer. Pancreas. 38:282–288. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Cohen AD and Kemeny NE: An update on hepatic arterial infusion chemotherapy for colorectal cancer. Oncologist. 8:553–566. 2003. View Article : Google Scholar : PubMed/NCBI
24.	Mocellin S, Pilati P, Lise M and Nitti D: Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol. 25:5649–5654. 2007. View Article : Google Scholar : PubMed/NCBI
25.	Homma H, Akiyama T, Mezawa S, et al: Advanced pancreatic carcinoma showing a complete response to arterial infusion chemotherapy. Int J Clin Oncol. 9:197–201. 2004. View Article : Google Scholar : PubMed/NCBI
26.	Miyanishi K, Ishiwatari H and Hayashi T: A phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for unresectable advanced pancreatic cancer after vascular supply distribution via superselective embolization. Jpn J Clin Oncol. 38:268–274. 2008. View Article : Google Scholar
27.	Mogami K, Ichihara T, Sato T, et al: A case of the papilla of vater accompanied witn a stricture of the celiac artery by the median arcuate ligament. Jpn J Gastroenterol Surg. 41:1588–1593. 2008. View Article : Google Scholar
28.	Kikuchi K and Kanno H: Comparison for blood levels and clinical effects between tablet and other dosage forms of 5-fluorouracil (5-FU). Gan To Kagaku Ryouho. 6:559–565. 1979.
29.	Maruyama S, Ando M and Watayo T: Concentration of 5-FU after hepatic artery infusion chemotherapy for liver metastases of colorectal cancer. Gan To Kagaku Ryouho. 30:1635–1638. 2003.PubMed/NCBI