Artery infusion, hepatic

Kornmann M, Link KH, Lenz H-J, Pil-lasch J, Metzger R, Butzer U et al. Thymidylate synthase is a predictor for response and resistance in hepatic artery infusion chemotherapy. Cancer Lett 1997 118 29-35. 

Fig. 1. Floxuridine radiosensitization—long-term freedom from liver progression for patients with nondiffuse primary hepatobiliary cancer treated with combined radiation therapy and hepatic artery infusion of floxuridine.

Ensminger WD, Rosowsky A, Raso V, et al. A clinical pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2 -deoxyuridine and 5-fluorouracil. Cancer Res 1978 38 3784—3792. 

Floxuridine (FUDR) is the nucleoside of 5-fluo-rouracil that is readily converted into 5-fluorouracil in vivo. It has similar pharmacological effects but is preferred to 5-fluorouracil for hepatic arterial infusions because it is more extensively metabolized in the liver than 5-fluorouracil, with less systemic toxicity. 

Fluorouracil is normally given intravenously (Table 55-3) and has a short metabolic half-life on the order of 15 minutes. It is not administered by the oral route because its bioavailability is erratic due to the high levels of the breakdown enzyme dihydropyrimidine dehydrogenase present in the gut mucosa. Floxuridine (5-fluoro-2 -deoxyuridine, FUDR) has an action similar to that of fluorouracil, and it is only used for hepatic artery infusions. A cream incorporating fluorouracil is used topically for treating basal cell cancers of the skin. 

Sato, T., Asanuma, Y., Hashimoto, M., Heianna, X, Kusano, T., Kuro-kawa, T., Yasui, O., Koyama, K. Efficacy of hepatic arterial infusion of prostaglandin El in the treatment of postoperative acute liver failure. - Report of a case. Hepato-Gastroenterol. 2000 47 846-850... 

Hohn, D., Melnick, J., Stasg, R., Altman, D., Friedman, M., Ignoffo, R., Ferrell, L., Lewis, B. Biliary sclerosing in patients receiving hepatic arterial infusions of floxuridine. J. Clin. Oncol. 1985 3 98-102... 

Daly, J.M., Kemeny, N., Oderman, R, Botel, X Long-term hepatic arterial infusion chemotherapy. Anatomic considerations, operative technique, and treatment morbidity. Arch. Surg. 1984 119 936-941... 

Hanazaki, K., Kawamura, N., Wakabayashi, M., Sodeyama, H., Yoko-yama, S., Sode, Y., Miyazaki, T. Long-term survivor with hver metastases from rectal cancer treated by hepatectomy after hepatic arterial infusion chemotherapy. Hepato-Gastroenterol. 1998 45 816—820... 

Heslln, M.J., Me na-Franco, H., Barker, M., Vickers, S.M., Aldrete, J., Urist, M,M. Colorectal hepatic metastases - Resection, local ablation, and hepatic artery infusion pump are associated with prolonged survival. Arch. Surg. 2001 136 318-323... 

Lorenz, M., Hochmuth, K., Muller, H.H. Hepatic arterial infusion of chemotherapy for metastatic colorectal cancer. New Engl. X Med. 2000 342 1525-1526... 

Nakagawa H, Kobayashi K, Tone T, Fukuda K, Shinn E, Mishima H, Yagyu T, Kobayashi T, Kikkawa N. [Combination of intra-hepatic arterial infusion of low-dose cisplatin and oral administration of high-dose doxyfluridine for patients with liver metastases of gastric cancer.] Gan To Kagaku Ryoho 1996 23(6) 783-5. 

There have been three studies of the effects of percutaneous ethanol injections in the treatment of hepatocellular carcinoma, either alone (12,13) or in combination with transcatheter arterial embolization (14). The procedure was effective and safe and improved long-term survival. Adverse effects were generally mild and of short duration, and commonly included abdominal pain, fever, intoxication (especially among non-drinkers), transient rises in serum transaminases, and chemical thrombosis of the tributary branch of the portal vein. Hepatic infarction has been reported in two patients with hepatocellular carcinoma after percutaneous ethanol injection of the tumors (15). Both patients had previously been treated with transcatheter arterial infusion using a suspension of styrene maleic acid neocarzinostatin, and the liver damage may have occurred through a combination of arterial damage due to the neocarzinostatin and vasculitis caused by flow of the injected ethanol into a portal vein branch. 

The principle of hepatic arterial infusion is based on the fact that hepatic tumors derive much of their blood supply from the hepatic artery, whereas the liver parenchyma receives its supply from the portal venous circulation. 

Acute and chronic cholecystitis has been reported after floxuridine hepatic artery infusion (3). Chemotherapy in this patient was associated with persistent epigastric pain with radiation to the back which was not accompanied by any fever or white blood cell elevation. Cholecystectomy showed a shrunken, thickened fibrotic gallbladder that was filled with thick, pasty, hemorrhagic material. There were no gallstones. 

Doria MI Jr, Doria LK, Faintuch J, Levin B. Gastric mucosal injury after hepatic arterial infusion chemotherapy with floxuridine. A chnical and pathologic study. Cancer 1994 73(8) 2042-7. 

Aldrighetti L, Arm M, Ronzoni M, Salvioni M, Villa E, Ferla G. Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine (FUdR) for liver metastases from colorectal cancer. Hepatogastroenterology 2001 48(41) 1302-7. 

Of 57 consecutive patients treated with implanted hepatic arterial infusion pumps with a regimen of alternating floxuridine (0.1 mg/kg/day for 7 days) followed by a weekly pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks), two developed biliary sclerosis and 12 had mild transient liver function abnormalities (103). The liver alone or in combination with another area was the site of first progression of disease in 40 patients. 

Goldberg JA, Kerr DJ, Watson DG, Willmott N, Bates CD, McKillop JH, McArdle CS. The pharmacokinetics of 5-fluorouracil administered by arterial infusion in advanced colorectal hepatic metastases. Br J Cancer 1990 61(6) 913-15. 

Severe hypophosphatemia with myocardial dysfunction was noted in patients receiving tumor necrosis factor alfa by continuous hepatic arterial infusion (SEDA-17, 433). 

Because approximately two-thirds of patients who undergo resection of hepatic metastases will have disease recurrence, adjuvant systemic and hepatic arterial infusion chemotherapy have been studied in an attempt to improve long-term outcomes. A randomized trial that compared 6 months of hepatic floxuridine and dexamethasone plus TV fluorouracil with leucovorin to TV fluorouracil with leucov-orin alone following resection of hepatic metastases in 156 patients showed improved 2-year DPS (86% vs. 72%) and hepatic recurrence-free survival at 2 years (90% vs. 60%) with the combined therapy. Many practitioners offer adjuvant chemotherapy to select patients following potentially curative hepatic resection, but further studies, especially those involving more active agents, are needed to determine an optimal treatment regimen. ... 

Infusional 5-FU/LV + oxaliplatin OR bolus orinfusional 5-FU/LV + irinotecan OR bevacizumab + 5-FU-based regimen or hepatic artery infusion systemic therapy (if hepatic disease only). If unable to tolerate oxaliplatin or irinotecan-combinatlon regimen, then capecitabine OR bolus 5-FU/LV. 

GITSG Gastrointestinal Tumor Study Group HAI hepatic artery infusion HD high-dose... 

Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 1999 341 2039-2048. 

Cohen AD, Kemeny NE. An update on hepatic arterial infusion chemotherapy for colorectal cancer. Oncologist 2003 8 553-566. 

Patt YZ, Hoque A, Lozano R, et al. Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin. J Clin Oncol 1997 15 1432-1438. 

Nicotinic acid in high doses may affect the cholescintigraphy because of poor extraction and elimination of the radiotracer (toxic effect on hepatocytes). Total parenteral nutrition may cause delayed or no visualization of the gallbladder, even in patients with no gallbladder disease caused by bile stasis and the formation of thick viscous jelly-like bile. Nonvisualization of the gallbladder may also be caused by hepatic artery infusion during chemotherapy. 

Floxuridine (FUdR) FUdR (fluorodeoxyuridine FUDR) is used primarily by continuous infusion into the hepatic artery for treatment of metastatic carcinoma of the colon or following resection of hepatic metastases, the response rate to such infusion is 40 to 50%, or double that observed with intravenous administration. Intrahepatic arterial infusion for 14 to 21 days may be used with minimal systemic toxicity. However, there is a significant risk of biliary sclerosis if this route is used for multiple cycles of therapy. Treatment should be discontinued at the earliest manifestation of toxicity (usually stomatitis or diarrhea) because the maximal effects of bone marrow suppression and gut toxicity will not be evident until days 7 to 14. 

Inaba Y, Aral Y, Matsueda K, Takeuchi Y, Aramaki T (2001) Right gastric artery embolization to prevent acute gastric mucosal lesions in patients undergoing repeat hepatic arterial Infusion chemotherapy. J Vase Interv Radiol 12 957-963... 

Presently, numerous palliative hepatic-directed therapies are available for the treatment of non-resectable liver tumors, including conformal radiation therapy, microsphere brachytherapy, hepatic arterial infusion chemotherapy, transarte-rial chemoembolization, radiofrequency ablation and combinations of these treatments. 

Stubbs et al. [59] R 100 Follow-up (median) 11 mos (0.1-76.6) Empiric method used activity (GBq) not reported Response rate 85% Most received concurrent hepatic artery infusion of 5FU... 

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