Mechanism-based improvement in the therapeutic selectivity of 5-FU prodrug alone and under conditions of metabolic modulation.
To compare the antitumor activity of Tegafur (150 mg/kg/day) with continuous intravenous infusion of 5-fluorouracil (5-FU) (12.5 mg/kg/day) and with oral UFT (60 mg/kg/day) with and without low- or high-dose leucovorin (50 or 200 mg/kg/day), rats with advanced colon cancer were treated with Tegafur or UFT 3 times daily for 28 days and 5-FU by continuous intravenous infusion for 28 days. UFT alone had a complete remission (CR) rate of 38%, whereas Tegafur and 5-FU produced no CRs. When high-dose leucovorin was added, the CR rate for UFT increased to 75%; Tegafur plus high-dose leucovorin resulted in only a partial remission rate of 50%, with no CRs; low-dose leucovorin was not as effective as the high dose. Hence, UFT clearly offers significant therapeutic advantages over Tegafur and protracted infusion of 5-FU. High-dose leucovorin is essential for significant modulation of drug action in this tumor.
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Roswell Park Cancer Institute, Buffalo, N.Y. 14263, USA.
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D002955:Leucovorin / Q000008:administration & dosage; D011355:Prodrugs / Q000008:administration & dosage; D051381:Rats; D005641:Tegafur / Q000008:administration & dosage* / Q000378:metabolism; D014498:Uracil / Q000008:administration & dosage*
D004338:Drug Combinations; D011355:Prodrugs; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil