Abstract
The role of thymidine in the treatment of cancer has been under clinical investigation for nearly a decade. Clinical trials have demonstrated that it lacks antitumor activity in its own right. In this review, the mechanism of action and rationale for the use of thymidine as a biochemical modulator of standard agents such as 5-fluorouracil, 1-beta-D-arabinofuranosylcytosine, and methotrexate are summarized. With this background, the clinical trials which have been conducted with thymidine, either alone or in combination, are described. We suggest a number of further studies of the role of thymidine in the biochemical modulation of antimetabolites.
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / administration & dosage
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Antimetabolites, Antineoplastic / metabolism
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Antimetabolites, Antineoplastic / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Aspartic Acid / administration & dosage
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Aspartic Acid / analogs & derivatives
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Aspartic Acid / pharmacology
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Cytarabine / administration & dosage
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Cytarabine / metabolism
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DNA Replication / drug effects
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DNA, Neoplasm / biosynthesis
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Deoxycytidine Kinase / antagonists & inhibitors
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Drug Evaluation
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Drug Synergism
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Fluorouracil / administration & dosage
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Fluorouracil / metabolism
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Folic Acid Antagonists
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Humans
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Interphase / drug effects
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Kinetics
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Leukemia / drug therapy
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Methotrexate / administration & dosage
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Methotrexate / pharmacology
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Mice
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / metabolism
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Nucleic Acid Synthesis Inhibitors
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Nucleotides / metabolism
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Phosphonoacetic Acid / administration & dosage
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Phosphonoacetic Acid / analogs & derivatives
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Phosphonoacetic Acid / pharmacology
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RNA, Neoplasm / biosynthesis
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Species Specificity
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Thymidine / administration & dosage
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Thymidine / adverse effects
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Thymidine / metabolism
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Thymidine / pharmacology*
Substances
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Antimetabolites, Antineoplastic
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DNA, Neoplasm
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Folic Acid Antagonists
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Nucleic Acid Synthesis Inhibitors
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Nucleotides
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RNA, Neoplasm
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Cytarabine
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Aspartic Acid
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sparfosic acid
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Deoxycytidine Kinase
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Phosphonoacetic Acid
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Fluorouracil
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Thymidine
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Methotrexate