Phase 1 pharmacokinetic study of the oral pan-AKT inhibitor MK-2206 in Japanese patients with advanced solid tumors.
Cancer Chemother Pharmacol
; 76(2): 409-16, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26104654
ABSTRACT
PURPOSE:
MK-2206 is an oral, highly selective inhibitor of AKT. The safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of MK-2206 was evaluated in Japanese patients with advanced solid tumors.METHODS:
Patients received a single oral dose of MK-2206 according to an every other day (QOD) dosing schedule or a once weekly (QW) dosing schedule in repeating 28-day treatment cycles, with a 7-day rest after only the first cycle. The dose-limiting toxicities (DLTs) were evaluated during Cycle 1. Full PK sampling was performed during Cycle 1.RESULTS:
Twenty-four patients were treated at 45 mg (n = 3) or 60 mg (n = 9) QOD or at 135 mg (n = 3) or 200 mg (n = 9) QW. One patient experienced a DLT at 60 mg QOD, and three patients experienced DLTs at 200 mg QW. No DLTs were observed at 45 mg QOD or at 135 mg QW. The DLTs included mucosal inflammation, hyponatremia, face edema, erythema multiforme, and hyperglycemia. Common adverse events related to MK-2206 included rash, an elevated insulin c-peptide level, stomatitis, pyrexia, eosinophilia, leukopenia, and hyperglycemia. PK differences in MK-2206 exposure were observed between Japanese patients and non-Japanese patients. The higher exposure in Japanese patients was likely caused by the relatively lower weight of Japanese patients versus non-Japanese patients. No tumor responses were observed, but six patients exhibited stable disease lasting longer than 4 months.CONCLUSIONS:
MK-2206 has an acceptable safety profile in Japanese patients with advanced solid tumors and warrants further investigation.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-akt
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Compostos Heterocíclicos com 3 Anéis
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Antineoplásicos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article