Percutaneous hepatic arterial infusion (HAI) of mitomycin C and floxuridine (FUDR): An effective treatment for metastatic colorectal carcinoma in the liver

Abstract

The response rate of metastatic colorectal carcinoma confined to the liver to HA1 of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HA1 to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m' administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography , and radio-nuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5-FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapy-related complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment Cancer 46:261-265, 1980. ETASTATIC COLORECTAL CARCINOMA confined to M the liver, refractory to intravenous chemo-therapy, will respond to hepatic arterial infusion (HAI) of chemotherapy.' Promising results have been reported with a combination of HA1 of floxuridine (FUDR) and hepatic r a d i a t i ~ n , ' ~ and HA1 of C. parvum and ~hemotherapy.~ When metastases are localized, partial liver resection is a valid consideration .Io The increased sensitivity of liver metastases to drugs administered intraarterially is the result of their ex-* Giora M. Mavligit, MD is a recipient of a PHS Career Development Award CA-00130-04. posure to higher concentrations of chemotherapy. Inactivation of these agents by the liver parenchyma occurs ~ubsequently.~ The blood leaving the liver through the hepatic veins contains lower drug levels ,* exposing normal tissues to lower drug concentrations and thereby lessening toxic side effects. Since mitomycin C (MTC) and FUDR have both activity in colon carcinoma3 and are inactivated by the liver,5 the combination of these chemotherapeutic agents exposes the liver metastases to very...

Gastric Dysplasia-Like Epithelial Atypia Associated with Chemoradiotherapy for Esophageal Cancer: A Clinicopathologic and Immunohistochemical Study of 15 Cases

“…In fact, atypical epithelial changes have been observed in some instances (19 -26). For example, hepatic arterial infusion chemotherapy has been reported as an effective method of treating both primary and metastatic colonic carcinoma of the liver (27,28). Interestingly, there have been several previously published reports of gastric and duodenal ulceration, with epithelial atypia, following this form of chemotherapy (19 -22, 24 -26).…”

Gastroduodenal artery‐duodenal fistula: A complication of continuous floxuridine (FUDR) infusion into the gastroduodenal artery

“…Peptic ulceration is not common with systemic chemotherapy [ 16,171, although gastritis, duodenitis, and ulceration have been reported in patients receiving intrahepatic chemotherapy whether infused by pump [ 3 - 6,18,19] or from percutaneous catheters [20,21]. Ulceration occurs in only 10-20% of the pump population, although many more may develop gastritis [22].…”

Hepatic Artery Infusion Chemotherapy for Liver Malignancy

“…Depending on the study, complication rates were reported to range anywhere from 30% to 79%. [40][41][42] These high rates in part reflect that unlike systemic cancer therapies, HAI chemotherapy is subject to both chemotherapyrelated toxicities and potential technical complications related to surgery, the HA infusion catheter, and the implanted pump.…”