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

Autor:	Greenhalf W; Affiliations of authors: Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK (WG, JPN, EG, TFC, PG, EC, CMH, CLR, FC, RJ); the Princess Margaret Hospital, Toronto, Canada (MJM); Manchester Academic Health Sciences Centre, Christie NHS Foundation Trust, School of Cancer and Enabling Sciences, University of Manchester, UK (JWV); Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK (DHP); Beatson West of Scotland Cancer Centre, Glasgow, UK (ACM); Glasgow Royal Infirmary, Glasgow, UK (RC); Hôpital Tenon, Université, Pierre et Marie Curie, Paris, France (FL); Austin Health, Melbourne, Australia (NCT); Prince of Wales Hospital and Clinical School University of New South Wales, New South Wales, Australia (DG); Nepean Cancer Centre and University of Sydney, Sydney, Australia (JS); Agia Olga Hospital, Athens, Greece (CD); Medical Oncology, Clatterbridge Centre for Oncology, Bebington, Merseyside, UK (DS); Department of Oncology, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden (BG); University Hospital, North Staffordshire, UK (MD); Freeman Hospital, Newcastle upon Tyne, UK (RMC); Service de Chirurgie Digestive et Viscérale, Hôpital Tenon, Paris, France (FL); Cross Cancer Institute and University of Alberta, Alberta, Canada (JRM, AGS); Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, UK (MRM); St James's University Hospital, Leeds, UK (AA); Department of Medicine A, University Medicine Greifswald, Greifswald, Germany (JM); Petz Aladar Hospital, Gyor, Hungary (AO); Departments of Surgery and Pathology and ARC-NET Research Center, University of Verona, Italy (AS, CB); Department of Surgery, University of Heidelberg, Heidelberg, Germany (MWB)., 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, Oláh A, Jackson R, Rawcliffe CL, Scarpa A, Bassi C, Büchler MW
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2014 Jan; Vol. 106 (1), pp. djt347. Date of Electronic Publication: 2013 Dec 03.
DOI:	10.1093/jnci/djt347
Abstrakt:	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 (χ(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 (χ(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 (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients. Conclusions: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.
Databáze:	MEDLINE
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