title: Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.
abstract: BACKGROUND
  Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy.
  
  
  METHODS
  Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR).
  
  
  RESULTS
  The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%).
  
  
  CONCLUSIONS
  FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Alain
authors.initials: A
authors.lastname: Gelibter
authors.forename: Paola
authors.initials: P
authors.lastname: Malaguti
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Enzo Maria
authors.initials: EM
authors.lastname: Ruggeri
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.forename: Fabio
authors.initials: F
authors.lastname: Carboni
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.forename: Mario
authors.initials: M
authors.lastname: Pellicciotta
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018395:CA-19-9 Antigen / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D000093542:Gemcitabine