Glaxo Wellcome Inc.

Smithkline Beecham Corporation

Burroughs Wellcome Co.

Adherex Technologies, Inc.

Elion Oncology LLC

Thomas Spector

Saad George Rahim

David J T Porter

Devron R Averett

Eric C Bigham

Virgil L Styles

Robert W Morrison, Jr

David J Porter

Donald W Kufe

Brian Huber

Todd A Blumenkopf

William Paul Peters

Todd A Blumenhopf

Donald J Nelson

Methods for improved administration and dosing of DPD inhibitors in combination with 5-FU and/or 5-FU prodrugs are provided, comprising first administering to a patient in need thereof a DPD inhibitor that substantially eliminates activity of the enzyme in both nervous and non-nervous tissues within the patient and thereafter administering 5-FU or a 5-FU prodrug, wherein the level of 5-FU or 5-FU generated from a prodrug is in substantial excess of DPD inhibitor in the patient.

Methods for preventing or reducing neurotoxicity associated with administering DPD inhibitors in combination with 5-FU and 5-FU prodrugs

Methods for improved administration and dosing of DPD inhibitors in combination with 5-FU and/or 5-FU prodrugs are provided, comprising first administering to a patient in need thereof a DPD inhibitor that substantially eliminates activity of the enzyme and thereafter administering 5-FU or a 5-FU prodrug, wherein the level of 5-FU or 5-FU prodrug is in substantial excess of DPD inhibitor in the patient.

Methods for administering DPD inhibitors in combination with 5-FU and 5-FU prodrugs

Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-flourouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, ido, cyano, halo-substituted Calkyl, Calkenyl, 1-halo-Calkenyl and halo-substituted Calkynyl.

Uracil reductase inactivators

This invention relates to pharmaceutical compositions of 5-alkynyluracil compounds in the form of tablets or capsules.

Pharmaceutical compositions of 5-alkynyl uracil compounds

Uracil reductase inactivators, notably a 5-substituted uracil or 5,6-dihydro-5-substituted uracil, potentiate 5-fluorouracil and find use particularly in the treatment of cancer. The 5-substituent is selected from bromo, iodo, cyano, halo-substituted C,alkyl, C,alkenyl, 1-halo-C,alkenyl and halo-substituted C,aklynyl.

Uracil reductase inactivatores

The present invention relates to a group of 5-substituted uracil derivatives which are inactivators of uracil reductase and which are particularly useful in cancer chemotherapy, especially in combination with antimetabolite antineoplastic agents such as 5-fluorouracil.

This application relates to pharmaceutical compositions of 5-alkynyl-dideoxyridbouracils which generates 5-alkynyluracils in vivo, which are inactivators of uracil reductase.

Pharmaceutical compositions of 5-alkynyl-dideoxyribouracil

This invention relates to pharmaceutical compositions of 5-alkynuracil.

The present invention relates to a group of 5-substituted uracil derivatives which are inactivators of uracil reductase and which are particularily useful in cancer chemotherapy, especially in combination with antimetabolite antineoplastic agents such as 5-fluorouracil (5-FU).

Pharmaceutical compositions containing 5-substituted uracil compounds are disclosed. The compositions are preferably in the form of a tablet or capsule.

Pharmaceutical compositions of 5-substituted uracil compounds

The present invention relates to novel ribonucleotide reductase inhibitors and new combinations comprising an antiviral compound, such as acyclovir, and a thiocarbonohydrazone ribonucleotide reductase inhibitor for the chemotherapeutic treatment of virus infections, especially viruses of the herpes group.

Antiviral combinations and compounds therefor

The present invention relates to novel ribonucleotide reductase inhibitors and new combinations comprising an antiviral compound, such as acyclovir, and a thiocarbonohydrazone ribonucleotide reductase inhibitor for the chemotherapeutic treatment of virus infections, espectially viruses of the herpes group.

Synergistic combinations of nucleoside analogues, which are converted to viral DNA polymerase inhibitors through the action of at least one virus-induced enzyme, and thiosemicarbazone ribonucleotide reductase inhibitors are especially useful in combatting herpes virus infections.

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Durham, NC, United States of America

Thomas Spector