Intra-arterial chemotherapy using an implantable infusion pump and liver irradiation for the treatment of hepatic metastases.

Liver metastases are a common cause of death in colon carcinoma. The dual blood supply of the liver permits regional perfusion while hepatic catabolism fo 5-fluorouracil (FU), floxuridine (FUdR) permit higher drug exposures than systemic (IV) administration. We have studied the effect of continuous intra-arterial chemotherapy (FU: 5-10 mg/kg/day and FUdR: 0.2 mg/kg/day) and whole liver irradiation (1000 rad every 4 weeks, total dose of 3000 rad) for metastatic colon carcinoma to liver. Eighteen patients with metastases to liver only are reported using this combination therapy. Seven patients had percutaneous placement of a catheter via the brachial artery, two had operative placement of a catheter via the gastroduodenal artery, all of which were connected to the Cormed infusor system, nine had operative placement of the Infusaid implantable pump with catheter placement into the hepatic artery via the gastroduodenal artery. The median survival for the entire group was 241 days. In those patients whose liver function tests (bilirubin and alkaline phosphatase) were less than two times normal, the median survival was 770 days. The median survival of the patients with greater than two times normal LFT's was 178 days. Two patients died of complications of the treatment. One who developed irreversible radiation hepatitis but at autopsy had only two areas of microscopic tumor foci in the liver and another who had received only 15 days of infusion and 1000 rad to liver. This patient developed irreversible chemical enteritis secondary to chemotherapy infusion into the superior mesenteric artery. Three patients have undergone abdominal reexploration and one at autopsy, who were found to have no gross evidence of tumor in the liver despite previous pathologic confirmation. It appears that some patients with minimal tumor burdens can have sterilization of their tumors. There were three cases of reversible liver function abnormalities. Complications associated with conventional intra-arterial chemotherapy (artery thrombosis, catheter sepsis and dislodgement, pump infusion variation and pump failure) were not seen with the Infusaid delivery system. The pump is refilled every 2-3 weeks via percutaneous puncture. All therapy was given on an outpatient basis. Pump acceptance and tolerance was 100%. Intra-arterial chemotherapy can now be accomplished without the morbidity associated with it in the past. The combination of chemotherapy and liver irradiation may offer improved survival in selected patients.