Phase I study of LY2603618, a CHK1 inhibitor, in combination with gemcitabine in Japanese patients with solid tumors.
Anticancer Drugs
; 26(10): 1043-53, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26288133
ABSTRACT
This phase I trial evaluated LY2603618, a selective inhibitor of the DNA damage checkpoint kinase 1, in combination with gemcitabine. Japanese patients with advanced solid tumors were enrolled. All patients received gemcitabine (1000 mg/m on days 1, 8, and 15 every 28 days) and either 170 mg (cohort 1) or 230 mg (cohort 2) of LY2603618. The primary objective was assessment of safety/tolerability. Pharmacokinetic/pharmacodynamic marker profiles were secondary objectives. Of the 17 patients enrolled, dose-limiting toxicities were observed in one patient in cohort 1 (n=7) and in two patients in cohort 2 (n=10). The most common grade 3 or more drug-related treatment-emergent adverse events were hematological. Three patients discontinued because of adverse events. Dose-dependent decreases in LY2603618 exposure were observed, but the LY2603618 pharmacokinetics at each dose were consistent within and between cycles and did not influence gemcitabine pharmacokinetics. Circulating plasma DNA decreased from baseline in all four patients who achieved a partial response. Administration of 170 or 230 mg of LY2603618 following a standard dose of gemcitabine showed acceptable safety and tolerability in Japanese patients with solid tumors.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
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Protocolos de Quimioterapia Combinada Antineoplásica
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Inibidores de Proteínas Quinases
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Neoplasias
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article