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: Alain Gelibter, Paola Malaguti, Serena Di Cosimo, Emilio Bria, Enzo Maria Ruggeri, Paolo Carlini, Fabio Carboni, Giuseppe Maria Ettorre, Mario Pellicciotta, Diana Giannarelli, Edmondo Terzoli, Francesco Cognetti, Michele Milella
• Journal: Cancer (Cancer) Vol. 104 Issue 6 Pg. 1237-45 (Sep 15 2005) ISSN: 0008-543X [Print] United States
• PMID: 16078261 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 American Cancer Society.

Chemical References

• CA-19-9 Antigen
• Deoxycytidine
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy)
• Biliary Tract Neoplasms (drug therapy, mortality)
• CA-19-9 Antigen (blood)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Female
• Humans
• Male
• Pancreatic Neoplasms (drug therapy, mortality)
• Survival Rate
• Gemcitabine