Abstract
Chemotherapy has remained the major treatment modality for patients with metastatic or recurrent colorectal carcinoma. The chemotherapeutic agent, 5-fluorouracil (FUra), has been the “standard” therapy for a number of years. The objective response rate for this single agent has been disappointing with most series reporting response rates between 12 and 20%. Recent studies involving intracellular pharmacokinetics of FUra have provided information concerning mechanisms which lead to cellular resistance to the active metabolite, FdUMP, which binds to intracellular thymidylate synthetase (TS). A number of recent studies have now been performed which suggest that increased levels of intracellular reduced folate analogs can overcome intracellular drug resistance to FdUMP.
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