Article (Scientific journals)
Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma.
Marechal, Raphael; Mackey, John R; Lai, Raymond et al.
2010In Cancer, 116 (22), p. 5200-6
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Keywords :
Adenocarcinoma/drug therapy/enzymology/surgery; Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine/analogs & derivatives/therapeutic use; Deoxycytidine Kinase/metabolism; Disease-Free Survival; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms/drug therapy/enzymology/metabolism/mortality/surgery; Treatment Outcome
Abstract :
[en] BACKGROUND: Gemcitabine (2',2'-difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease-free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine-based chemoradiation regimen. METHODS: Forty-five patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based-therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK-positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values. RESULTS: The median follow-up was 19.95 months (95% confident interval [CI], 3.3-107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66-7.31; P = .001; OS: HR, 3.2; 95% CI,1.44-7.13; P = .004). CONCLUSIONS: dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Marechal, Raphael
Mackey, John R
Lai, Raymond
Demetter, Pieter
Peeters, Marc
Polus, Marc ;  Centre Hospitalier Universitaire de Liège - CHU > Gastro-Entérologie-Hépatologie
Cass, Carol E
Salmon, Isabelle
Deviere, Jacques
Van Laethem, Jean*-Luc
Language :
English
Title :
Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma.
Publication date :
2010
Journal title :
Cancer
ISSN :
0008-543X
eISSN :
1097-0142
Publisher :
Wiley, Hoboken, United States - New Jersey
Volume :
116
Issue :
22
Pages :
5200-6
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2010 American Cancer Society.
Available on ORBi :
since 12 February 2011

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