Gemcitabine and capecitabine synergism and biomodulation with dipridamole in a mouse tumor model

12034 Background and Aim: Gemcitabine and capecitabine are antimetabolites that are effective in the pyrimidine pathway of the DNA synthesis. Capecitabine through a 3-step activation process is transformed to 5-FU in the tumor cell by thymidine phosphorilase. On the other hand, gemcitabine interacts with the enzymes thymidine kinase, tymidine phosphorilase ve ribonucloetide reductase. Our hypothesis is based on a possible synergistic blockade by concurrent administration of these two antimetabolites. Additionally, dipridamole is an inhibitor of the nucleoside transport; and that can prolong the accumulation of antimetabolites within the tumor cell. In this study, combinations of these drugs are tested on an animal model. Methods and Results: 80 male balb-c mice were inoculated dorsally with 0.1 cc Ehrlich ascites tumor, and 10 days later the animals were separated into 5 groups having a similar tumor load. The control group received no treatment, while in the gemcitabine arm the animals received 50 mg/d gemcitabine on day 1. In the capecitabine arm, the animals received 1mg/day capecitabine administered in drinking water on days 1–4. In the gemcitabine + capecitabine combination arm, the animals received both treatments. In the gemcitabine + capecitabine + dipridamole arm, in addition to both of the drugs, dipridamole was also given 2mg/day in drinking water on days 1–4. In the control group (n=16) median survival was 17 days, while it was 33 days in gemcitabine arm (n=11), 35 days in capecitabine arm (n=14), and 44 days in the gemcitabine + capecitabine combination arm (n=22) which was significantly higher (p<0.007). Dipridamole added to this combination (n=17) did not prolong survival any further. Conclusion: combination of gemcitabine with capecitabine suggests favorable results in an animal model. Testing of this combination in clinical trials seems to be justified. No significant financial relationships to disclose.