Intra-arterial Floxuridine vs Systemic Fluorouracil for Hepatic Metastases From Colorectal Cancer

Martin, J. Kirk

doi:10.1001/archsurg.1990.01410200086013

Cited by 347 publications

(121 citation statements)

References 17 publications

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“…The remaining five studies (Kemeny M et al, 1986;Chang et al, 1987; Kemeny N et al, 1987;Hohn et al, 1989;Martin et al, 1990) compared intra-arterial therapy with conventional systemic chemotherapy. Overall, 41% of patients receiving intra-arterial treatment responded compared with only 14% of those receiving systemic treatment.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

Howell

McArdle²,

Kerr³

et al. 1997

Br J Cancer

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Summary Forty patients with unresectable colorectal metastases confined to the liver were evaluated in a phase 11 study. 5-Fluorouracil (5-FU) was delivered via a surgically placed hepatic artery catheter. Patients received folinic acid (200 mg m-2) intravenously over 2 h followed by a loading dose of intra-arterial 5-FU (400 mg m-2) over 15 min, then 5-FU (1600 mg m-2) by intra-arterial infusion over the following 22 h. This was repeated on day 2 and the whole schedule was repeated every 2 weeks. Response was assessed after six treatments. The median follow-up was 17 months. Overall response rate was 46% with 8% complete response. Estimated median survival is 19 months. Site of progression was the liver alone in 55%, liver and lung in another 16% and 29% in other sites. Eight patients experienced grade 3 or 4 toxicity. The response rate of this regimen compares favourably with reported trials of intra-arterial FUDR, and our schedule is currently being compared with a similar schedule of intravenous 5-FU and folinic acid in a randomized Medical Research Council trial (CR05).Keywords: colorectal cancer; liver metastases; chemotherapy; infusion intra-arterial Colorectal cancer is the second most common cause of cancer deaths in the UK. Approximately half of the patients undergoing apparently curative resection will die within 5 years because of recurrent disease, mostly with liver metastases; in 30% of these patients the liver will be the only site affected. Few patients are suitable for surgical treatment, most having multiple metastases affecting both lobes. Unfortunately, the results of conventional systemic chemotherapy have been disappointing. For example, single-agent 5-flourouracil (5-FU) has a response rate of approximately 10% (Blijham et al, 1996). Furthermore, although the addition of folinic acid (FA) to 5-FU has resulted in higher response rates, there remains doubt as to whether this translates into a survival benefit (Advanced Colorectal Cancer Meta-analysis Project, 1992).As most cytotoxic drugs have a steep dose-response curve, it is a basic pharmacokinetic principle that if one can increase drug delivery to a tumour then increased response rates can be achieved (Gamelin et al, 1995). An alternative approach to the therapy of liver metastases is therefore to deliver the drug intra-arterially. In the case of patients with liver metastases the arterial route of delivery is particularly appropriate as it has been shown that established liver metastases over 1 cm in diameter are mainly supplied by the hepatic artery (Breedis, 1954).We report our experience of an intra-arterial 5-FU-based regimen in patients with unresectable colorectal liver metastases. In this study, we combined three factors that, on the basis of pharmacological studies, have been shown to offer a therapeutic advantage, namely intra-arterial administration, infusional rather Received 17 February 1997 Revised 9 April 1997 Accepted 29April 1997 Correspondence to: JD Howell than bolus 5-FU therapy and modulation of 5-FU by high-dose ...

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Section: Discussionmentioning

confidence: 99%

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

Howell

McArdle²,

Kerr³

et al. 1997

Br J Cancer

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“…It is clear that intrahepatic chemotherapy is an effective therapy and is associated with a significantly higher number of responses than systemic chemotherapy. [42][43][44][45][46][47] The response rates for HAI were 48 to 62 percent, compared with zero to 21 percent for intravenous therapy. Critics have pointed out that this increase in response rate has translated to increased survival in only one study.…”

Section: Regional Infusional Therapymentioning

confidence: 99%

Surgical treatment of colorectal metastases to the liver

Fong

Blumgart

Cohen

1995

CA: A Cancer Journal for Clinicians

124

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“…These abnormalities might have been produced by release of inflammatory mediators from liver parenchyma (Jenkins and Williams, 1980) or liver metastases (Ueda et al, 1994). Hepatic parenchymal volume is not reduced by colorectal liver metastases (Dworkin et al, 1 995a), and it is also possible that catheterization-induced hepatic arterial thrombosis resulted in parenchymal necrosis where portal venous flow was impeded by metastases (Martin et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Hepatic arterial cannulation for regional chemotherapy is safe in patients with a liver metastasis volume of less than 1 litre

Burke

Fordy²,

Earlam³

et al. 1997

Br J Cancer

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Summary Hepatic arterial cannulation for regional chemotherapy was achieved in 121/134 (90.2%) of colorectal liver metastasis patients. The perioperative mortality (5.8%) was significantly greater (P = 0.004) in patients with > 1000 ml (5/22, 23%) compared with < 1000 ml (2/83, 2.4%) metastasis volume. Colorectal liver metastasis patients should be considered for regional chemotherapy before metastases become extensive.Keywords: colorectal liver metastasis; hepatic artery cannulation; regional chemotherapy Metastasis resection cures 5% of patients with colorectal liver metastases (Steele and Ravikumar, 1989) but for the rest, tumour growth produces abdominal pain and distension, jaundice and inferior vena caval compression, resulting in death at an average of 7 months from liver metastasis diagnosis (Wood, 1980; AllenMersh et al, 1994). Continuous hepatic arterial floxuridine infusion prevents clinically significant liver metastasis growth in 70% of patients (Dworkin and Allen-Mersh 1991; Allen-Mersh et al, 1994), and doubles survival compared with patients receiving symptom palliation (Piedbois et al, 1996). Although the hepatic artery can be cannulated percutaneously by inserting a Seldinger wire via the axillary or femoral artery under fluoroscopy, longterm treatment has not been possible with this approach because of catheter dislodgement and misperfusion of adjacent structures (Cohen et al, 1983). These difficulties can be avoided by direct insertion of the catheter at laparotomy, but the limited survival benefit of hepatic arterial floxuridine could be impaired by complications from open hepatic artery cannulation.This study assessed the morbidity and mortality in colorectal liver metastasis patients undergoing hepatic arterial cannulation at laparotomy and identified patient-or disease-related characteristics that were associated with a complicated outcome. MATERIALS AND METHODSAll colorectal liver metastasis patients undergoing hepatic arterial cannulation in one unit between March 1988 and January 1996 were assessed. All had unresectable liver metastases with no evidence of extrahepatic disease after primary tumour removal, on abdominal computerized tomography (CT) scan and chest radiograph.Received 20 June 1996 Revised 11 November 1996 Accepted 14 November 1996 Correspondence to: TG Allen-Mersh, Department of Surgery, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Exclusion criteria were patient age > 75 years, Karnofsky performance < 60, serum bilirubin > 20 mmol 1-1 or ascites.Liver metastasis volume was measured from CT scan (Dworkin et al, 1995a). Any weight loss in the month before hepatic artery cannulation was noted. Serum liver function tests, albumin, creatinine and full blood count were measured before and after operation. Physical symptoms were assessed by the Rotterdam Symptom Checklist (De Haes et al, 1990) before and at monthly intervals after operation.At laparotomy via a subcostal incision, an Infusaid (Infusaid, Norwood, MA, USA) arterial cannula was insert...

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Intra-arterial Floxuridine vs Systemic Fluorouracil for Hepatic Metastases From Colorectal Cancer

Cited by 347 publications

References 17 publications

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

A phase II study of regional 2-weekly 5-fluorouracil infusion with intravenous folinic acid in the treatment of colorectal liver metastases

Surgical treatment of colorectal metastases to the liver

Hepatic arterial cannulation for regional chemotherapy is safe in patients with a liver metastasis volume of less than 1 litre

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