Low hENT1 Is Associated With Poorer Survival in Patients With Pancreatic Cancer Receiving Adjuvant Gemcitabine


Key Points

  • Low hENT1 expression was associated with significantly poorer survival in gemcitabine-treated patients.
  • hENT1 expression was not significantly associated with survival in fluorouracil/leucovorin recipients or observation patients.

In a study reported in the Journal of the National Cancer Institute, Greenhalf et al analyzed the association between human equilibrative nucleoside transporter 1 (hENT1) levels and survival in patients with pancreas cancer receiving adjuvant gemcitabine or fluorouracil (5-FU)/leucovorin after resection in the ESPAC-3 trial. Low hENT1 level was associated with significantly poorer survival in gemcitabine recipients.

Study Details

The study involved analysis of 1,808 core samples from 352 patients randomly assigned to gemcitabine or 5-FU/leucovorin and 28 control patients who received neither regimen. hENT1 expression was determined using 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).

Median overall survival for the 176 gemcitabine patients and 176 5-FU/leucovorin patients included in the analysis was 23.4 months vs 23.5 months (P = .62). High hENT1 levels were present in 74 (51%) of 146 patients who died in the gemcitabine group, 60 (43%) of 139 who died in the 5-FU/leucovorin group, and 18 (78%) of 23 who died in the observation group. The only tumor or patient characteristic that was significantly associated with hENT1 level was age, with low hENT1 levels being more common in patients aged ≥ 64 years (P = .02).

Reduced Survival in Gemcitabine Group

Median overall survival was 17.1 months for patients with low hENT1 expression vs 26.2 months in those with high expression in the gemcitabine group (χ2= 9.87,  P = .002). Median overall survival was 25.6 months for patients with low hENT1 expression vs 21.9 months in those with high expression in the 5-FU/leucovorin group (χ21 = 0.83,  P = .36), and hENT1 levels were also not predictive of survival in the 28 patients in the observation group (χ21  = 0.37, P = .54). On multivariate analysis adjusting for resection margin status, lymph node status, tumor grade, sex, and smoking, hENT1 level remained a significant predictor in the gemcitabine group (Wald χ2 = 9.16, P = .003) but not in the 5-FU/leucovorin group (Wald χ2 = 1.22, P = .27).

Analysis of recurrence-free survival produced similar results. Median recurrence-free survival was 11.1 months in those with low hENT1 expression vs 14.3 months in those with high expression in the gemcitabine group  (χ2 = 7.45, P = .006) and 12.5 vs 12.8 months in the 5-FU/leucovorin group (χ2 = 1.43, P = .23).

The investigators concluded, “Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.”

J. P. Neoptolemos, MD, of University of Liverpool, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by Cancer Research UK and Liverpool NIHR Pancreas Biomedical Research Unit. The study authors reported no potential conflicts of interest.

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