Method of administrating an anticancer drug containing α, α, α-trifluorothymidine and thymidine phosphorylase inhibitor

Abstract

The present invention relates to a method for treating a cancer comprising orally administering a composition containing α,α,α-trifluorothymidine (FTD) and 5-chloro-6-(1-(2-iminopyrrolidinyl)methyl)uracil hydrochloride in a molar ratio of 1:0.5 at a dose of 20 to 80 mg / m2 / day in terms of FTD in 2 to 4 divided portions per to patients in need of the treatment.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]This is a reissue application of U.S. Pat. No. 7,799,783, issued from application Ser. No. 11 / 042,059, filed Jan. 26, 2005. FIELD OF THE INVENTION[0002]The present invention relates to a method for treating cancer, providing an increased therapeutic effect against cancer, which comprises administering an anticancer drug that uses α,α,α-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI) in combination.BACKGROUND OF THE INVENTION[0003]α,α,α-Trifluorothymidine (FTD, see the structural formula below) is a nucleoside analogue with substitution of a methyl group to trifluoromethyl group at the 5-position of thymidine, which was synthesized by Heidelberger et al. (J. Am. Chem. Soc., 84: 3597-3598, 1962; J. Med. Chem., 7: 1-5, 1964).[0004][0005]Unlike a fluorouracil (FU)-based antitumor drug that are widely used for cancer patients, FTD has no effect on RNA, and is phosphorylated by an intracellular thymidine kinase to form a...

AI Technical Summary

Benefits of technology

This approach significantly increases antitumor activity and improves therapeutic outcomes while reducing the total daily dose, maintaining effective FTD levels in DNA and managing side effects, as demonstrated in clinical trials and animal models.

Problems solved by technology

Clinical trials of FTD were performed in 1970s, revealing the problem inherent in FTD that this drug is degraded by a thymidine phosphorylase (TP) in a human body after intravenous administration, resulting in the extremely shortened half-life thereof in the blood, i.e. approximately 12 minutes (Cancer Res., 32: 247-253, 1972).

Further, although some tumor regressions were noted by divided doses every three hours, several problems have been also indicated that this means of administration lacks general usage, have showed adverse invent of the bone marrow supression and gastrointentinal toxicities, and have not necessarily been able to contribute to survival period even in some patients having tumor shrinkage (Cancer Chemother. Rep., 55: 205-208, 1971).

However, the resultant therapeutic effect of this combination drug against cancer was not satisfactory in the trial.

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