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gemcitabine + fluorodeoxyuridine + leucovorin is a combination chemotherapy regimen investigated by the National Cancer Institute (NCI) for the treatment of advanced solid tumors and lymphomas. The regimen utilizes the synergistic effects of three agents: gemcitabine, a nucleoside analog that inhibits ribonucleotide reductase and competes with dCTP for incorporation into DNA; fluorodeoxyuridine (floxuridine), a pyrimidine analog that is converted to fluorodeoxyuridine monophosphate (FdUMP) to potently inhibit thymidylate synthase; and leucovorin (calcium folinate), which acts as a biochemical modulator to stabilize the binding of FdUMP to thymidylate synthase, thereby enhancing the inhibition of DNA synthesis. This specific Phase I study was designed to evaluate the safety, toxicities, and maximum tolerated dose of sequential gemcitabine followed by a 24-hour continuous infusion of fluorodeoxyuridine and oral leucovorin.
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