Gemcitabine has been combined with 5-FU, and may enhance the activity of 5-FU in vivo. Gemcitabine is an inhibitor of ribonucleotide reductase, an enzyme needed for synthesis of deoxynucleotides, and 5-FU interferes with dTTP synthesis by inhibition of thymidylate synthase (TS). It is plausible that concomitant administration of gemcitabine and capecitabine, may result in increased cytotoxicity by reducing intracellular dTTP thru two different mechanisms, thereby inhibiting DNA replication and repair. Platinum compounds lead to cell death by forming DNA adducts and causing double strand breaks. By inhibiting DNA synthesis and repair, both gemcitabine and 5-FU analogues could potentiate the activity of carboplatin. These interactions may underlie the clinical synergism that has been observed with platinum/5-FU and platinum/gemcitabine combinations.