High Expression of hENT1 Can Predict Better Survival Among Patients on Postsurgical Gemcitabine

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High levels of expression of the human equilibrative nucleoside transporter 1 (hENT1) were associated with longer median survival of patients with pancreatic adenocarcinoma receiving gemcitabine, according to an analysis of clinical data and cancer tissue collected from the European Study Group for Pancreatic Cancer (ESPAC)-3 trial. That trial found that after resection for pancreatic ductal carcinoma, adjuvant gemcitabine was not superior to fluorouracil (5-FU)/leucovorin.

The final analysis included 380 patients, 176 in each of the two treatment groups, and 28 in the observation group. Levels of hENT1 were not predictive of survival for patients in the observation group.

The median age of patients was 64, and 59.5% were male. The median number of days from surgery to randomization was 49, and 75.7% of patients had standard resection, 14.3% had radical resection, and 9.9% had extended radical resection.

Study Data

The study showed that although patients treated with gemcitabine vs 5-FU/leucovorin had similar median overall survivals (23.4 vs 23.5 months), median survival for patients treated with gemcitabine was 26.2 months for those with high hENT1 expression vs 17.1 months for those with low hENT1 expression (P = .002), a difference of 9.1 months. For patients receiving 5-FU/leucovorin, median survival was 21.9 months for those with high hENT1 expression vs 25.6 for those with low hENT1 expression (P = .36).

“Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ2 = 9.16; P = .003) but not [5-FU]–treated (Wald χ2 = 1.22; P = .27) patients,” the ESPAC researchers reported. Calling hENT1 a “promising biomarker,” the investigators explained that it “permits the bidirectional passage into cells of pyrimidine nucleosides,” such as gemcitabine
and 5-FU.

Results were reported in the Journal of the National Cancer Institute. The chief investigator was John P. Neoptolemos, MD, of the Liverpool Cancer Research UK Centre, United Kingdom.

“Taken together, the results of this study have provided powerful evidence that adjuvant gemcitabine should not be used after resection for patients with low tumor hENT1 expression, the alternative being 5FU-based regimens, and by implication vice versa,” the researchers concluded. They also stated that their study “paves the way for the introduction of hENT1 assessment for a stratified medicines approach in pancreatic cancer, not only in the adjuvant setting but also potentially in the advanced setting.”

Greenhalf W, et al: J Natl Cancer Inst 106(1):djt347, 2014.