title: Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial.
abstract: BACKGROUND
  Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6-month survival, response, and toxicity associated with a combination of gemcitabine, 5-fluorouracil (5-FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA).
  
  
  METHODS
  A 4-week course included 1000 mg/m2 gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25 mg/m2 LV by intravenous push, and 600 mg/m2 5-FU by intravenous push after LV.
  
  
  RESULTS
  Forty-two patients were enrolled in 6 months, 35 of whom had metastatic disease. Patients with biliary tract ACA included 24 with hepatic disease (19 patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4 with disease in the ampulla of Vater. All patients were evaluable and received a median of 4 courses of treatment (range, 1-21 courses). Commonly occurring severe toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea (four patients), fatigue (seven patients), thrombocytopenia (six patients), emesis (four patients), and diarrhea (four patients). Five partial responses (9.5%) occurred, 3 of which were sustained for > or = 8 weeks. No treatment-related deaths occurred. Thirty-two patients had disease progression and 38 died after a median follow-up of 20 months (range, 1.4-24 months). The median time to disease progression was 4.6 months (95% confidence interval [95% CI], 2.4-6.6%). The median survival period was 9.7 months (95% CI, 7-12%).
  
  
  CONCLUSIONS
  This combination regimen was manageable in patients with advanced biliary tract and gallbladder ACA. Of 42 patients, 24 (57%) survived > or = 6 months, satisfying the primary end point of the trial. The length of survival suggested that gemcitabine, 5-FU, and LV had benefit equivalent to gemcitabine alone.
authors.affiliation: Division of Medical Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. alberts.steven@mayo.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
authors.forename: Hani
authors.initials: H
authors.lastname: Al-Khatib
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Mahoney
authors.forename: Lawerence
authors.initials: L
authors.lastname: Burgart
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cera
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Tom R
authors.initials: TR
authors.lastname: Finch
authors.forename: Ralph
authors.initials: R
authors.lastname: Levitt
authors.forename: Harold E
authors.initials: HE
authors.lastname: Windschitl
authors.forename: James A
authors.initials: JA
authors.lastname: Knost
authors.forename: Loren K
authors.initials: LK
authors.lastname: Tschetter
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine