Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.

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Neutralization of Acidic Tumor Microenvironment (TME) with Daily Oral Dosing of Sodium Potassium Citrate (K/Na Citrate) Increases Therapeutic Effect of Anti-cancer Agent in Pancreatic Cancer Xenograft Mice Model

PURPOSE Although the susceptibility to chemotherapy of unresectable/advanced pancreatic cancer is very poor, the usefulness of new anticancer drugs, such as S-1, has been reported in recent years. We clinically investigated whether or not S-1 would prolong survival in this study. OBJECTIVE 17 unresectable pancreatic cancer patients who came for consultation between November 2001 and August 2008 (ten men, seven women). The average age was 72.5 years and performance statuses before medical treatment were 0-2. METHOD A group of 8 patients did not use S-1 (non-S-1 group) and a group of a patients (S-1 group)did. The average survival period, one-year survival rate, and hospitalization rate were examined. RESULT The average survival period of the non-S-1 group was 173.1 days, and its one-year survival rate was 12.5%, compared to 435.1 days and 55.6% in the S-1 group. The hospitalization rate was 25.6% in the S-1 group, against 53.1% in the non-S-1 group. DISCUSSION S-1 treatment for unresectable/advanced pancreatic cancer served to prolong the survival period, suggesting it enabled extension of the recuperation-at-home period.

[Effectiveness of S-1 therapy for unresectable/advanced pancreas cancer].

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[Effectiveness of S-1 therapy for unresectable/advanced pancreas cancer].