Therapy for metastatic colorectal cancer with hepatic artery infusion chemotherapy using a subcutaneous implanted pump.

Abstract

Sixty-two patients with metastatic colorectal carcinoma involving the liver were treated by hepatic intra-arterial chemotherapy using an implantable infusion pump. The 53 patients with metastases confined to the liver had a median survival (MS) of 17 months and an objective response rate of 32%. Four patients (8%) demonstrated a complete response (CR), with normal abdominal computed tomography (CT) scan results and plasma carcinoembryonic antigen (CEA) levels, and 13 patients (25%) demonstrated a partial response (PR), with at least a 50% decrease in the liver lesions by CT scan and at least a 50% decrease in CEA levels. Thirty patients (57%) had stable disease (S), and six patients (11%) had no response (NR). Nine patients with extrahepatic tumor plus hepatic metastases had an MS of only 4.9 months. None of these patients had an objective response, and only four patients had S. Quality of response was clearly associated with longevity. Forty patients treated with floxuridine (FUDR) and mitomycin (M) (F + M) showed a 20% objective response rate, while the 13 patients treated with FUDR and dichloromethotrexate (DCMTX) (F + D) attained a 69% objective response rate. Although F + D treatment appears to be superior, there may have been selection biases that make such an observation only preliminary. Twenty-six (49%) of the 53 patients developed hepatitis during infusion chemotherapy, which resolved after temporary cessation of the chemotherapy. Of the 17 patients with CR or PR, 12 patients (71%) had hepatitis, whereas only 14 (39%) of the 36 patients with S or NR had hepatitis. Eleven patients had evidence of peptic ulceration by endoscopic examination during the infusion chemotherapy. All the ulcers healed after chemotherapy was discontinued.

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

“…As a result, regional infusion of the hepatic artery with percutaneous catheters was attempted clinically as early as 1964 but infection and mechanical complications with these catheters led to the implantation of drug infusion pumps in the late 1980s. Several studies have examined their clinical use, reporting favourable tumour responses ranging from 29 to 88 % (Buchwald et al 1980;Balch et al 1983;Cohen et al 1983;Shepard et al 1985). A randomized clinical trial comparing tumour response for systemic vs regional (intra-arterial) delivery of chemotherapy also suggested improvement for regional therapy.…”

Hepatotoxicity of Chemotherapy

“…Toxicity appears to be both time-and dose-dependent. With rare exceptions, the hepatitis picture usually improves with the temporary cessation of chemotherapy, but the development of secondary sclerosing cholangitis is irreversible [46,47]. Two patterns of sclerosis may be seen: a diffuse pattern and the diffuse pattern plus short segments of tight stricture, usually located in the proximal bile ducts [48].…”

Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver.

“…1,2 Early clinical trials documented the ability of intrahepatic FUDR to produce regression of hepatic metastases, [3][4][5][6][7] and subsequent controlled trials indicated that tumor response rates were higher with intrahepatic FUDR compared with single-agent systemic (intravenous) fluorouracil (5-FU) or FUDR.8-1 2 However, there has been no convincing demonstration of an improvement in survival with the use of intrahepatic FUDR compared with the use of systemic chemotherapy in this patient population 13 due in large measure to the development of extrahepatic sites of metastatic disease that are left untreated by regional chemotherapy. It would therefore be rational to add a systemic therapy in combination with regional hepatic chemotherapy to suppress or eradicate occult metastases outside the liver.…”