Oral fluoropyrimidines in the treatment of colorectal cancer.
5-Fluorouracil (5-FU) has been the mainstay of systemic therapy for colorectal cancer since its initial development 40 years ago. Efforts to improve the therapeutic index of 5-FU have included alteration of schedule and addition of biochemical modulators. An understanding of 5-FU mechanisms of action has resulted in major therapeutic advances in the past 10 years; however, a plateau has been reached in the efficacy of 5-FU, mandating a paradigm shift for those involved in colorectal cancer drug development. One direction vigorously pursued is the development of orally administered fluoropyrimidines that maintain or improve upon the effectiveness of intravenous 5-FU. In this paper the preclinical and clinical development of oral fluoropyrimidines and their modulators is reviewed, including UFT, capecitabine, ethynyluracil and S-1.
Meropol
N J
NJ
Division of Medical Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D042943:Dihydrouracil Dehydrogenase (NADP); D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D011725:Pyridines; C096910:UFT(R) drug; D003841:Deoxycytidine; D005641:Tegafur; C073482:eniluracil; D014498:Uracil; D000069287:Capecitabine; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil; C104201:gimeracil