Combination chemo-radiation therapy for jaundice due to focal malignant obstruction of the major bile ducts.

Twenty patients with focal malignant obstruction of the major bile ducts (6 cholangiocarcinoma, 8 colorectal, 3 hepatoma, 2 unknown primary, and 1 gastric cancer) were treated on a protocol examining the toxicity and efficacy in relieving jaundice of external beam radiation therapy (4500 cGy in 300 cGy fractions) combined with continuous hepatic arterial (15 patients) or peripheral venous (5 patients) fluorouracil infusion. Toxicity of this regimen consisted of anorexia with mild nausea and vomiting in 55% of patients and gastric ulceration (responsive to medical management) in 15% of patients. One patient exhibited transient grade 2 hepatic toxicity and one had asymptomatic grade 4 leukopenia. Of 14 patients treated without prior biliary drainage, 8 exhibited a decrease in bilirubin levels from a mean of 14.5 mg/dl to 1.5 mg/dl. Four of six patients with biliary drainage catheters at the start of treatment were able to have them removed without reobstruction. For the 8 responding patients among those who did not have cholangiocarcinomas, the median response duration was 5 months with a median survival from treatment of 6.5 months. For the 4 responding patients with cholangiocarcinoma, the median response duration was 16 months with a median survival from treatment of 20 months. All responders did not have a return of jaundice due to reobstruction of the major ducts (until death or to the present). All responders who have died did so due to tumor progression outside of the treated field except for one who died of unrelated causes. The mean number of proven or presumed episodes of cholangitis per patient was virtually identical in those without (1.8) and those with stents/tubes (1.4, p = 0.561). This regionally focused combined modality cytotoxic therapy was able to relieve obstruction in the majority of patients without excess morbidity (including a lack of any detectable increase in sepsis). Thus, it appears feasible to consider randomized studies of this cytotoxic approach versus standard mechanical drainage procedures to define the relative risks and benefits of each.