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HENT1 tumor levels to predict survival of pancreatic ductal adenocarcinoma patients who received adjuvant gemcitabine and adjuvant 5FU on the ESPAC trials.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Some studies in patients with resected pancreatic cancer have suggested that expression of the human equilibrative nucleoside transporter (hENT1) may be predictive of improved survival from gemcitabine but these have either been based on retrospective non-randomized studies or in one study the principal treatment was chemoradiation. The samples collected from the adjuvant ESPAC1/3 randomized trials have provided a unique opportunity to assess to REMARK standards the therapeutic predictability of hENT1 in patients undergoing resection for pancreatic cancer. Methods: Tissue Microarrays (TMAs) were prepared using paraffin embedded tumor specimens from patients randomized to gemcitabine or 5FU/Folinic acid in the ESPAC-1 and -3 trials. Cores were given an H-Score depending on the level of staining with the 10D7G2 anti-hENT1 antibody. Groups were compared using Kaplan-Meier and Cox proportional hazards. Results: Scores were obtained for 176 gemcitabine treated and 176 5FU treated patients. The overall median H-Score was 48 and patients were classified as having high hENT1 if the mean score for their cores was above this. Median overall survival for gemcitabine treated patients was 23.4 (95% CI: 18.3, 26.0) months versus 23.5 (95% CI: 19.8, 27.3) months for 5FU treated patients (χ21 = 0.24, P = 0.623). In the gemcitabine group A significantly lower survival (χ21 = 9.87, P = 0.002) was noted with low hENT1 (median survival 17.1 (95% CI: 14.3, 23.8) versus 26.2 (95% CI: 21.2, 31.4) months). Median survival was 25.6 (95% CI: 20.1, 27.9) and 21.9 (95% CI: 16.0, 28.3) months respectively for high and low hENT1 in the 5FU group, a non-significant difference (χ21 = 0.83, P = 0.362). Multivariate analysis confirmed hENT1 expression as a predictive marker in gemcitabine (Wald χ2 = 7.10, P = 0.008) but not 5-fluorouracil (Wald χ2 =0.34, P = 0.560) groups. Conclusions: The study supports use of gemcitabine in patients with high tumor hENT1 expression and 5-fluorouracil in patients with low hENT1.