Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial

William Greenhalf, Paula Ghaneh, John P. Neoptolemos, Daniel H. Palmer, Trevor F. Cox, Richard F. Lamb, Elizabeth Garner, Fiona Campbell, John R. MacKey, Eithne Costello, Malcolm J. Moore, Juan W. Valle, Alexander C. McDonald, Ross Carter, Niall C. Tebbutt, David Goldstein, Jennifer Shannon, Christos Dervenis, Bengt Glimelius, Mark DeakinRichard M. Charnley, François Lacaine, Andrew G. Scarfe, Mark R. Middleton, Alan Anthoney, Christopher M. Halloran, Julia Mayerle, Attila Oláh, Richard Jackson, Charlotte L. Rawcliffe, Aldo Scarpa, Claudio Bassi, Markus W. Büchler

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Abstract

BackgroundHuman equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.MethodsMicroarrays 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.ResultsThree 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 (χ2 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 (χ21= 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 (χ21 = 0.83; P =. 36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ21 = 0.37; P =. 54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P =. 003) but not 5-fluorouracil-treated (Wald χ2 = 1.22; P =. 27) patients.ConclusionsSubject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Original languageEnglish
Article numberdjt347
JournalJournal of the National Cancer Institute
Volume106
Issue number1
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Greenhalf, W., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., Lamb, R. F., Garner, E., Campbell, F., MacKey, J. R., Costello, E., Moore, M. J., Valle, J. W., McDonald, A. C., Carter, R., Tebbutt, N. C., Goldstein, D., Shannon, J., Dervenis, C., Glimelius, B., ... Büchler, M. W. (2014). Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. Journal of the National Cancer Institute, 106(1), [djt347]. https://doi.org/10.1093/jnci/djt347