High-Dose Weekly Oral Leucovorin and 5-Fluorouracil in Previously Untreated Patients with Advanced Colorectal Carcinoma: A Phase I Study
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.
KeywordsThymidylate Synthetase Indicator Lesion Advanced Colorectal Carcinoma Leucovorin Calcium Oral Leucovorin
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