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- Title
Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial.
- Authors
Greenhalf, William; Ghaneh, Paula; Neoptolemos, John P.; Palmer, Daniel H.; Cox, Trevor F.; Lamb, Richard F.; Garner, Elizabeth; Campbell, Fiona; Mackey, John R.; Costello, Eithne; Moore, Malcolm J.; Valle, Juan W.; McDonald, Alexander C.; Carter, Ross; Tebbutt, Niall C.; Goldstein, David; Shannon, Jennifer; Dervenis, Christos; Glimelius, Bengt; Deakin, Mark
- 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 hENTl-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 (χ²1=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). Fortheö-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. Conclusions Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.
- Subjects
NUCLEOSIDES; NUCLEOTIDES; PANCREATIC cancer genetics; CANCER genetics; ANTINEOPLASTIC agents
- Publication
JNCI: Journal of the National Cancer Institute, 2014, Vol 106, Issue 1, p1
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djt347