Oral fluoropoyrimidines.
Protracted intravenous infusions of fluorouracil (5-FU) in the treatment of colorectal cancer have been associated with a reduction in toxicity and enhanced clinical activity compared with bolus 5-FU schedules. However, these protracted infusions require portable infusion pumps and central venous lines, which are associated with complications of venous thrombosis, infection, and line slippage. An effective oral 5-FU formulation could provide a more convenient protracted treatment method with fewer complications. Because of its inconsistent and erratic absorption, the use of oral 5-FU was abandoned decades ago. The inconsistent absorption of oral 5-FU may be attributed to varying levels of dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Two methods have been used to circumvent 5-FU's metabolism by DPD in the gastrointestinal tract. First, DPD may be inactivated, allowing for reliable, consistent absorption of 5-FU. Second, 5-FU prodrugs can be administered, being absorbed as intact molecules via the gastrointestinal tract and subsequently converted to 5-FU. The oral fluoropyrimidines discussed here are capable of providing prolonged 5-FU exposure with a reduced incidence of toxicity.
Hoff
P M
PM
Division of Medicine, The University of Texsas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Royce
M
M
Medgyesy
D
D
Brito
R
R
Pazdur
R
R
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP); D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D005493:Folic Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology / Q000627:therapeutic use; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010094:Oxonic Acid / Q000494:pharmacology / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D005641:Tegafur / Q000494:pharmacology / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D011355:Prodrugs; D011725:Pyridines; C096910:UFT(R) drug; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; C073482:eniluracil; D014498:Uracil; D010094:Oxonic Acid; D000069287:Capecitabine; C053194:Emitefur; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil