Phase I first-in-human study of TAK-285, a novel investigational dual HER2/EGFR inhibitor, in cancer patients.
Br J Cancer
; 106(4): 666-72, 2012 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-22240796
ABSTRACT
BACKGROUND:
This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2.METHODS:
The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks.RESULTS:
In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d.CONCLUSION:
The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Prevencao_e_fatores_de_risco
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Agentes_cancerigenos
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Receptor ErbB-2
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Compostos Bicíclicos Heterocíclicos com Pontes
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Receptores ErbB
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Hidroxibutiratos
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Neoplasias
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Antineoplásicos
Tipo de estudo:
Clinical_trials
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Japão