A pilot study was designed to evaluate the efficacy of high-dose
FUDR administered through the hepatic artery for the treatment of
cancer involving the liver. Three dose schedules were used beginning with a dose of 0.5 mg
FUDR/kg/day for 2 weeks followed by
normal saline infusion for 2 weeks (schedule A). Elevation of serum
bilirubin was the sole indication to deescalate to schedule B (0.3 mg
FUDR/kg/day for two weeks followed by saline infusion for 4 weeks). Tolerance to this schedule escalated the patient to schedule C (0.5 mg
FUDR/kg/day for 2 weeks followed by
normal saline infusion for 4 weeks). Eighteen patients were treated, sixteen with metastatic
colon cancer, one with metastatic
leiomyosarcoma, and one with
hepatoma. The patient with
hepatoma developed progressive disease after one cycle of
therapy. Of the 17 patients with metastatic
cancer only 5 patients failed
therapy yielding a 70% response rate. High-dose
FUDR was well tolerated with only six patients requiring deescalation to schedule B. Elevation of
alkaline phosphatase and
glutamic oxaloacetic transaminase was universal. Two patients developed peptic ulceration.
Sclerosing cholangitis was not observed. We conclude that high-dose
FUDR administered through the hepatic artery is as safe as conventional dose infusion
therapy but probably not more effective. The safety of high-dose
FUDR infusion
therapy suggests that
sclerosing cholangitis is association with hepatic arterial infusion
therapy is not related to the
FUDR dose.