Intra-arterial continuous infusion for treatment of pancreatic and biliarytract cancer - A dose-escalation study of fluorouracil combined with gemcitabine

Background. Systemic chemotherapy does not satisfactorily improve the poor prognosis of pancreas and biliary tract cancer unresectable or metastatic t o the liver. Intra-arterial infusion of antineoplastic agents can give high er concentrations to the tumor and slighter concentrations to the whole bod y, with a potential of efficacy and lower toxicity, due to the hepatic clea rance. Methods. Based on a safe and ambulatorial technique of transcutaneous arter ial port implantation, this study was designed to evaluate feasibility and toxicity of 5-fluorouracil (5-FU) intra-arterial continuous infusion combin ed with systemic gemcitabine with dose escalation. Seventeen patients affec ted by pancreatic (14) or biliary tract (3) cancer received up to six cycle s of treatment. Treatment consisted of intravenous gemcitabine on d 1 and 8 and intra-arterial 5-FU continuous infusion on d 1-14 every 21 d. Dose-esc alation levels were 900 and 1000 mg/m(2) for gemcitabine and 8, 10, 12, 15, and 17 mg/kg/d for 5-FU. Consecutive cohorts of three patients were planne d at each dose level. Results. Gastrointestinal toxicity (vomiting and diarrhea [3rd-4th degree] and gastritis), constituted the dose-limiting toxicity, with a maximum-tole rated dose of 1000 mg/m2 for gemcitabine and 15 mg/kg/d for 5-FU. Hematolog ical toxicity was present in a minority of patients. No patient had acute o r later complications such as arterial thrombosis related to the implanted arterial port, sclerosis cholangitis, or chemical cholecistitis. Conclusion. 5-Fluorouracil intra-arterial continuous infusion, combined wit h systemic gemcitabine, seems to be a feasible and safe regimen that could give interesting results in pancreatic cancer.