A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial.

Abstract

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.

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

“…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.…”

Surgical treatment of colorectal metastases to the liver

“…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.…”

Hepatic arterial floxuridine as second-line treatment for systemic fluorouracil-resistant colorectal liver metastases

“…HAI might be a useful secondline treatment in patients >-hose colorectal lixer metastases haxe become resistant to sx stemic fluorouracilUfolinic acid. Response to HAI has been reported in comparatixve studies of sx stemic xs hepatic arterial floxuridine (Kemeny et al 1987: Hohn et al 1989.…”