Regional chemotherapy of colorectal cancer metastatic to the liver

Abstract

Ninety‐three patients with biopsy‐proven colorectal cancer metastatic to the liver were treated with hepatic arterial infusion of 5‐fluorodeoxyuridine (FUDR). There were 52 men and 41 women (median age, 60 years). Forty‐two patients (45%) had failed prior systemic chemotherapy. Catheters were operatively placed and multiple catheters were used if dictated by hepatic arterial anatomy in order to obtain perfusion of the entire liver. The drug was delivered by a totally implanted INFUSAID model 400 pump and patients received cyclic therapy consisting of 2 weeks of 0.3 mg/kg/d FUDR alternating with 2 weeks of saline. Patients with extrahepatic tumor or patients whose hepatic tumor failed to respond to FUDR were given a 30 minute intraarterial infusion of mitomycin C, 15 mg/m2, every 6 to 8 weeks in addition to FUDR. Fifty of the 93 evaluable patients presented with metastatic tumor confined to the liver. Of these 50 patients, 83% demonstrated a significant reduction in tumor size with a median duration of response of 13 months and a median survival of 25 months from diagnosis of liver metastases. Twenty‐four of these 50 patients remain alive. Forty‐three patients presented with extrahepatic metastases in addition to their liver tumor, and 74% had a response with a median duration of 6 months and a median survival of 14 months. Only six patients of those presenting with extrahepatic tumor remain alive. None of the 93 patients died solely of uncontrolled liver tumor, and only 9 died as a result of uncontrolled liver metastases and disseminated extrahepatic tumor. The duration of survival for both groups was determined by the uncontrolled progression of extrahepatic tumor. In patients with metastatic colorectal cancer involving only the liver, hepatic arterial FUDR alone and with the addition of mitomycin C provided excellent control of hepatic tumor. Survival appeared to be prolonged in this uncontrolled study. Cancer 53:1336‐1343, 1984.

Surgical treatment of colorectal metastases to the liver

“…Currently, intra-arterial infusional chemotherapy appears to be an effective method for treatment of unresectable metastatic disease isolated to the liver. [37][38][39][40][41] Percutaneous catheters placed through the femoral artery have been used as a method to deliver chemotherapy into the hepatic artery. However, this method of delivery has been associated with a high incidence of gastrointestinal complications due to perfusion of the stomach or duodenum by branches of the hepatic artery.…”

A dog model using an implanted system for protracted hepatic arterial chemotherapy

“…The implantable Infusaid pump and catheter drug delivery system is being used increasingly for the regional administration chemotherapy in cancer patients on a chronic basis. For patients with primary and metastatic carcinomas within the liver, the application of regional chemotherapy with this system has resulted in reports of markedly improved response rates and perhaps has impacted upon survival [ 12,131. At the present time, however, the number of drugs and therapeutic modalities available for common use with the pump are extremely limited.…”

Hepatic arterial chemotherapy for metastatic colorectal carcinoma

“…However, in these and previous non-randomised regional chemotherapy studies, between 40 and 80% of patients treated with regional chemotherapy for solitary hepatic metastases develop extrahepatic recurrence from which most patients ultimately die (Niederhuber et al, 1984). In addition, of particular concern is the unacceptably high degree of local toxicity associated with regional FUDR.…”