Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
;
: 835-842, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-715974
ABSTRACT
PURPOSE:
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors. MATERIALS ANDMETHODS:
Standard 3+3 dose escalation scheme using two different dosing schedules were studied once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.RESULTS:
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Dose-limiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).CONCLUSION:
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Agendamento de Consultas
/
Fosfotransferases
/
Prurido
/
Neoplasias Gástricas
/
Estomatite
/
Tirosina
/
Técnicas In Vitro
/
Proteínas Tirosina Quinases
/
Neoplasias da Mama
/
Farmacocinética
Tipo de estudo:
Estudo de etiologia
/
Estudo de incidência
/
Estudo observacional
/
Fatores de risco
Limite:
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2018
Tipo de documento:
Artigo
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