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Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial

Lookup NU author(s): Richard Charnley

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Abstract

Background Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.Methods Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided.Results Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (chi(2)(1)=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (chi(2)(1)=9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (chi(2)(1) = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (chi(2)(1) = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald chi(2)(1) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald chi(2)(1) = 1.22; P = .27) patients.Conclusions Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.


Publication metadata

Author(s): Greenhalf W, Ghaneh P, Neoptolemos JP, Palmer DH, Cox TF, Lamb RF, Garner E, Campbell F, Mackey JR, Costello E, Moore MJ, Valle JW, McDonald AC, Carter R, Tebbutt NC, Goldstein D, Shannon J, Dervenis C, Glimelius B, Deakin M, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Halloran CM, Mayerle J, Olah A, Jackson R, Rawcliffe CL, Scarpa A, Bassi C, Buchler MW, European Study Group Pancreatic Cancer

Publication type: Article

Publication status: Published

Journal: JNCI-Journal of the National Cancer Institute

Year: 2014

Volume: 106

Issue: 1

Print publication date: 01/01/2014

Online publication date: 03/12/2013

Acceptance date: 29/09/2013

ISSN (print): 0027-8874

ISSN (electronic): 1460-2105

Publisher: Oxford Universtiy Press

URL: http://dx.doi.org/10.1093/jnci/djt347

DOI: 10.1093/jnci/djt347


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Funding

Funder referenceFunder name
Canadian Cancer Society
Cancer Council of South Australia
Cancer Councils of Victoria
Health and Medical Research Council of Australia
Australasian Gastro-Intestinal Trials Group
Cancer Council of New South Wales
Cancer Council of Queensland
Fondazione Italiana Malattie del Pancreas
Fonds de Recherche de la Societe Nationale Francaise de Gastroenterologie
Liverpool NIHR Pancreas Biomedical Research Unit
National Cancer Institute of Canada
Oxford NIHR Biomedical Research Centre
00/006Cancer Research UK
6421Associazione Italiana Ricerca Cancro (AIRC Regione Veneto)
C245/A82390Cancer Research UK
SP1984/0204Cancer Research UK
SP2590/0101Cancer Research UK

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