Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree

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

Research output: Contribution to journalArticle

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/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). 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/m2 demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.

Original languageEnglish
Pages (from-to)1237-1245
Number of pages9
JournalCancer
Volume104
Issue number6
DOIs
Publication statusPublished - Sep 15 2005

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gemcitabine
Biliary Tract
Pancreas
Carcinoma
Confidence Intervals
Carbohydrates
Therapeutics
Antigens
National Cancer Institute (U.S.)
Tumor Biomarkers
Transaminases
Neutropenia
Treatment Failure
Disease-Free Survival
Anemia
Adenocarcinoma
Multivariate Analysis
Survival Rate
Pharmacokinetics

Keywords

  • Biliary tree carcinoma
  • Carbohydrate antigen 19-9
  • Fixed dose rate
  • Gemcitabine
  • Pancreatic carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree. / Gelibter, Alain; Malaguti, Paola; Di Cosimo, Serena; Bria, Emilio; Ruggeri, Enzo Maria; Carlini, Paolo; Carboni, Fabio; Ettorre, Giuseppe Maria; Pellicciotta, Mario; Giannarelli, Diana; Terzoli, Edmondo; Cognetti, Francesco; Milella, Michele.

In: Cancer, Vol. 104, No. 6, 15.09.2005, p. 1237-1245.

Research output: Contribution to journalArticle

Gelibter, A, Malaguti, P, Di Cosimo, S, Bria, E, Ruggeri, EM, Carlini, P, Carboni, F, Ettorre, GM, Pellicciotta, M, Giannarelli, D, Terzoli, E, Cognetti, F & Milella, M 2005, 'Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree', Cancer, vol. 104, no. 6, pp. 1237-1245. https://doi.org/10.1002/cncr.21286
Gelibter, Alain ; Malaguti, Paola ; Di Cosimo, Serena ; Bria, Emilio ; Ruggeri, Enzo Maria ; Carlini, Paolo ; Carboni, Fabio ; Ettorre, Giuseppe Maria ; Pellicciotta, Mario ; Giannarelli, Diana ; Terzoli, Edmondo ; Cognetti, Francesco ; Milella, Michele. / Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree. In: Cancer. 2005 ; Vol. 104, No. 6. pp. 1237-1245.
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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/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). 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/m2 demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.",
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T1 - Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree

AU - Gelibter, Alain

AU - Malaguti, Paola

AU - Di Cosimo, Serena

AU - Bria, Emilio

AU - Ruggeri, Enzo Maria

AU - Carlini, Paolo

AU - Carboni, Fabio

AU - Ettorre, Giuseppe Maria

AU - Pellicciotta, Mario

AU - Giannarelli, Diana

AU - Terzoli, Edmondo

AU - Cognetti, Francesco

AU - Milella, Michele

PY - 2005/9/15

Y1 - 2005/9/15

N2 - 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/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). 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/m2 demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.

AB - 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/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). 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/m2 demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.

KW - Biliary tree carcinoma

KW - Carbohydrate antigen 19-9

KW - Fixed dose rate

KW - Gemcitabine

KW - Pancreatic carcinoma

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