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Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree
Article first published online: 2 AUG 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 6, pages 1237–1245, 15 September 2005
How to Cite
Gelibter, A., Malaguti, P., Di Cosimo, S., Bria, E., Ruggeri, E. M., Carlini, P., Carboni, F., Ettorre, G. M., Pellicciotta, M., Giannarelli, D., Terzoli, E., Cognetti, F. and Milella, M. (2005), Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree. Cancer, 104: 1237–1245. doi: 10.1002/cncr.21286
- Issue published online: 31 AUG 2005
- Article first published online: 2 AUG 2005
- Manuscript Accepted: 11 MAY 2005
- Manuscript Revised: 26 FEB 2005
- Manuscript Received: 20 OCT 2004
- Italian Ministry of Health. Grant Number: R.F. 02/184
- fixed dose rate;
- pancreatic carcinoma;
- biliary tree carcinoma;
- carbohydrate antigen 19-9
Gemcitabine infusion at the fixed dose rate of 10 mg/m2 per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy.
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/m2). 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).
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%).
FDR-gemcitabine at the weekly dose of 1000 mg/m2 demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. Cancer 2005. © 2005 American Cancer Society.