Optimal treatment regimens for 5'-deoxy-5-fluorouridine, with or without (E)-5-(2-bromovinyl)-2'-deoxyuridine, against various tumors in mice
- PMID: 2142152
- PMCID: PMC5918056
- DOI: 10.1111/j.1349-7006.1990.tb02586.x
Optimal treatment regimens for 5'-deoxy-5-fluorouridine, with or without (E)-5-(2-bromovinyl)-2'-deoxyuridine, against various tumors in mice
Abstract
The antitumor activity of 5'-deoxy-5-fluorouridine (DFUR), a prodrug of 5-fluorouracil (5-FU), is markedly enhanced if DFUR treatment is combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). Combined oral administration of DFUR (10 mg/kg) and BVDU (10 mg/kg) three times (every 3 h) per day for 5 days afforded greater antitumor activity than a single dose of DFUR (300 mg/kg/day) for 5 days in mice bearing either adenocarcinoma 755 or Lewis lung carcinoma, while in the colon 26 system the antitumor effects of both treatment regimens were equivalent. Thus, a low-dose regimen of DFUR when combined with BVDU provides a similar or greater antitumor activity than a high-dose regimen of DFUR that is not combined with BVDU. The area under the curve of plasma 5-FU following a treatment with the combination of DFUR (10 mg/kg) and BVDU (10 mg/kg) was equal to that following DFUR (300 mg/kg) treatment.
References
-
- ) Iigo , M. , Araki , E. , Nakajima , Y. , Hoshi , A. and De Clercq , E.Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5‐fluorouracil against adenocar‐cinoma 755 in mice. Increased therapeutic index and correlation with increased plasma 5‐fluorouracil levels . Biochem. Pharmacol. , 37 , 1609 – 1613 ( 1988. ). - PubMed
-
- ) Armstrong , R. D. and Diasio , R. B.Selective activation of 5′‐deoxy‐5‐fluorouridine by tumor cells as basis for an improved therapeutic index . Cancer Res. , 41 , 4891 – 4894 ( 1981. ). - PubMed
-
- ) Au , J. L‐S. , Rustum , Y. M. , Minowada , J. and Srivastave , B. I. S.Differential selectivity of 5‐fluorouracil and 5′‐deoxy‐5‐fluorouridine in cultured human B lymphocytes and mouse L1210 leukemia . Biochem. Pharmacol. , 32 , 541 – 546 ( 1983. ). - PubMed
-
- ) Ishitsuka , H. , Miwa , M. , Takemoto , K. , Fukuoka , K. , Itoga , A. and Maruyama , H. B.Role of uridine phosphorylase for antitumor activity of 5′‐deoxy‐5‐fluorouridine . Gann , 71 , 112 – 123 ( 1980. ). - PubMed
-
- ) Iigo , M. , Nishikata , K. , Nakajima , Y. , Hoshi , A. , Okudaira , N. , Odagiri , H. and De Clercq , E.Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5′‐deoxy‐5‐fluorouridine against adenocarcinoma 755 in mice: correlation with pharmacokinetics of plasma 5‐fluorouracil levels . Biochem. Pharmacol. , 38 , 1885 – 1889 ( 1989. ). - PubMed
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