title: Intra-arterial continuous infusion for treatment of pancreatic and biliary tract cancer.
abstract: BACKGROUND
  Systemic chemotherapy does not satisfactorily improve the poor prognosis of pancreas and biliary tract cancer unresectable or metastatic to the liver. Intra-arterial infusion of antineoplastic agents can give higher concentrations to the tumor and slighter concentrations to the whole body, with a potential of efficacy and lower toxicity, due to the hepatic clearance.
  
  
  METHODS
  Based on a safe and ambulatorial technique of transcutaneous arterial port implantation, this study was designed to evaluate feasibility and toxicity of 5-fluorouracil (5-FU) intra-arterial continuous infusion combined with systemic gemcitabine with dose escalation. Seventeen patients affected by pancreatic (14) or biliary tract (3) cancer received up to six cycles 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-escalation levels were 900 and 1000 mg/m2 for gemcitabine and 8, 10, 12, 15, and 17 mg/kg/d for 5-FU. Consecutive cohorts of three patients were planned at each dose level.
  
  
  RESULTS
  Gastrointestinal toxicity (vomiting and diarrhea [3rd-4th degree] and gastritis), constituted the dose-limiting toxicity, with a maximum-tolerated dose of 1000 mg/m2 for gemcitabine and 15 mg/kg/d for 5-FU. Hematological toxicity was present in a minority of patients. No patient had acute or later complications such as arterial thrombosis related to the implanted arterial port, sclerosis cholangitis, or chemical cholecistitis.
  
  
  CONCLUSIONS
  5-Fluorouracil intra-arterial continuous infusion, combined with systemic gemcitabine, seems to be a feasible and safe regimen that could give interesting results in pancreatic cancer.
authors.affiliation: Division of Surgical Oncology, Azienda Ospedaliera Sarn Giovanni Battista, Torino, Italy. zanoncl@tin.it
authors.forename: C
authors.initials: C
authors.lastname: Zanon
authors.forename: O
authors.initials: O
authors.lastname: Alabiso
authors.forename: M
authors.initials: M
authors.lastname: Grosso
authors.forename: R
authors.initials: R
authors.lastname: Buosi
authors.forename: I
authors.initials: I
authors.lastname: Chiappino
authors.forename: R
authors.initials: R
authors.lastname: Clara
authors.forename: A
authors.initials: A
authors.lastname: Satolli
authors.forename: S
authors.initials: S
authors.lastname: Zai
authors.forename: M
authors.initials: M
authors.lastname: Bortolini
authors.forename: M
authors.initials: M
authors.lastname: Botta
authors.forename: A
authors.initials: A
authors.lastname: Mussa
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine