Immunohistochemical analysis of human equilibrative nucleoside transporter-1 (hENT1) predicts survival in resected pancreatic cancer patients treated with adjuvant gemcitabine monotherapy.

BACKGROUND: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic cancer. Human equilibrative nucleoside transporter-1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. The aim of this study was to retrospectively determine the relationship between the outcome of pancreatic cancer after surgery followed by postoperative gemcitabine monotherapy and the expression of hENT1. METHODS: A total of 27 resected pancreatic cancer patients treated with adjuvant gemcitabine were analyzed for tumor hENT1 expression via an immunohistochemical analysis. The staining intensity and the percentage of positive tumor cells were scored, and the composite score (hENT1 score) was obtained by obtaining the sum of these two scores. RESULTS: There were 11 patients assigned to the low hENT1 expression group, and 16 patients to the high hENT1 group. The patients with tumors that had higher hENT1 expression had a significantly longer disease-free survival (DFS) (log rank, P = 0.022) and overall survival (OS) (P = 0.024). The hENT1 expression was indicated to be a significant and independent prognostic factor for OS by the univariate (P = 0.030) and multivariate analyses (P = 0.019). CONCLUSIONS: A high expression of hENT1 in pancreatic cancer was found to be significantly associated with a longer survival in patients who received adjuvant gemcitabine monotherapy after curative resection, and hENT1 immunohistochemistry may well serve as a significant prognostic factor for these patients.

Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for resected pancreatic cancer.

BACKGROUND: The factors which affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated in pancreatic cancer. The objective of this retrospective study was to clarify the risk factors for the discontinuation of S-1 adjuvant chemotherapy after 6 months of treatment. METHODS: The study included patients who underwent curative surgery for pancreatic cancer, were diagnosed with stage II or III disease, had a serum creatinine level ≤1.2 mg/dl and received adjuvant S-1 between June 2007 and March 2014. RESULTS: Forty patients were eligible for the present study. A comparison of the 6-month continuation stratified by each clinical factor using the log-rank test revealed a significant difference in the creatinine clearance (CCr) between the patients who continued and discontinued the treatment. A CCr of 60 ml/min was regarded as a critical point. The uni- and multivariate Cox's proportional hazard analyses demonstrated that the CCr was the only significant independent predictive factor. The 6-month continuation rate was 70.8 % in the patients with a CCr ≥60 ml/min and was 25.0 % in patients with a CCr <60 ml/min (P = 0.008). The patients with a CCr <60 ml/min developed adverse events more frequently and earlier than those with a CCr ≥60 ml/min. CONCLUSIONS: A CCr < 60 ml/min was a significant risk factor for the 6-month discontinuation of S-1 adjuvant chemotherapy in pancreatic cancer patients, even though the renal function was judged to be normal based on the serum creatinine level. Careful attention is therefore required to improve the S-1 continuation in patients with a CCr < 60 ml/min.