Totally implanted drug delivery system for hepatic arterial chemotherapy

Abstract

A totally implanted drug delivery system for hepatic arterial chemotherapy was evaluated in 13 patients with metastatic (11 colon and one carcinoid) or primary (one hepatoma) cancer of the liver. During laparotomy, a Silastic catheter was positioned in the hepatic artery for infusion to the entire liver arterial vasculature as ascertained by low-flow radionuclide angiography with 99Tc-macroaggregated albumin. The catheter was connected to a subcutaneously implanted model 400 Infusaid pump (Metal Bellows Corp, Sharon, MA). Each pump had a 50-ml volume and a set rate (3--6 ml/day) and required refill every 8--16 days. A side port bypassed the pumping mechanism and allowed direct catheter injection for nuclide angiography, for bolus drug administration, or for clearing of a blocked catheter. Pump refills and side port injections were performed by percutaneous injection. The 13 patients in this ongoing study received a median of 6 months (range, 4.5--17) of continuous hepatic arterial infusion. The pump performed reliably with stable (+/- 10%) flow rates and only one malfunction in 2800 cumulative days of use. Flow distribution determined by low-flow radionuclide angiography did not change in 12 patients. Patient acceptance was excellent, with the ability to participate fully in normal daily activities. Eleven patients showed partial hepatic tumor regressions documented by physical examination and nuclide liver scans. All patients were treated with 5-fluorodeoxyuridine. Two patients failed 5-fluorodeoxyuridine therapy and subsequently responded briefly to dichloromethotrexate. This implanted system should facilitate future investigation of regional chemotherapy using these and other agents.