First-in-human, phase I dose-escalation study of single and multiple doses of a first-in-class enhancer of fluoropyrimidines, a dUTPase inhibitor (TAS-114) in healthy male volunteers

• Published in: Cancer chemotherapy and pharmacology Vol. 73; no. 3; pp. 577 - 583
• Main Authors: Saito, Kaku, Nagashima, Hirotaka, Noguchi, Kazuharu, Yoshisue, Kunihiro, Yokogawa, Tatsushi, Matsushima, Eiji, Tahara, Takeshi, Takagi, Shigeru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2014; Springer; Springer Nature B.V
• Subjects: Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Biological and medical sciences; Cancer Research; Cohort Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - pharmacokinetics; Healthy Volunteers; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pyrophosphatases - antagonists & inhibitors; Young Adult; 5-Fluorouracil; dUTPase; First-in-human study; DPD; PK; Safety; CYP3A4; Antineoplastic agent; Cytochrome CYP3A4; Dose escalation; Isozyme; Toxicity; Multiple dose; pK; Fluorouracil; Human; Healthy subject; Enzyme; Transferases; Cytochrome P450; Fluoropyrimidine derivatives; Single dose; Enzyme inhibitor; ); Dihydropyrimidine dehydrogenase (NADP; Thymidylate synthase; dUTP pyrophosphatase; Antimetabolic; Methyltransferases; Phase I trial; Pyrimidine derivatives; Hydrolases; Oxidoreductases

Purpose TAS-114 is a first-in-class oral deoxyuridine triphosphatase (dUTPase) inhibitor, which acts as a modulator of the pyrimidine nucleotide metabolic pathway. This was a first-in-human, phase 1 study that investigated the pharmacokinetics (PK) and safety of single-agent TAS-114 when it was give...