Effects of STAT3 polymorphisms and pharmacokinetics on the clinical outcomes of gefitinib treatment in patients with EGFR-mutation positive non-small cell lung cancer.
J Clin Pharm Ther
; 45(4): 652-659, 2020 Aug.
Article
em En
| MEDLINE
| ID: mdl-32402096
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE:
We investigated the correlations among signal transducer and activator of transcription 3 (STAT3) rs4796793C >G polymorphism, gefitinib pharmacokinetics and clinical responses in Japanese patients with non-small cell lung cancer receiving gefitinib therapy.METHODS:
Forty-five patients were enrolled in this study. Plasma trough concentrations (C0 ) of gefitinib at the steady-state were measured by high-performance liquid chromatography. RESULTS ANDDISCUSSION:
Patients having a gefitinib C0 of at least ≥200 ng/mL had significantly longer PFS than patients having a C0 of <200 ng/mL (median [95% confidence interval (CI)] PFS 11.0 [8.2-13.7] and 5.3 [0.0-12.0] months, respectively, P = .042). There were no significant differences in PFS between patients with STAT3 rs4796793C/C and G alleles; however, patients with STAT3 rs4796793C/C having a gefitinib C0 of ≥ 200 ng/mL had significantly longer progression-free survival (PFS) and overall survival (OS) than those with a C0 of <200 ng/mL (median [95% CI] PFS 11.4 [4.1-18.6] and 3.0 [0.0-7.0] months, respectively, P = .008; median [95% CI] OS 20.6 [7.4-33.7] and 12.6 [10.1-15.1] months, respectively, P = .042). In patients with the STAT3 rs4796793G allele, there were no significant differences in PFS and OS between the two gefitinib C0 groups. In addition, there were no significant differences in PFS or OS according to smoking, presence of proton pump inhibitor combination, or onset of side effects. WHAT IS NEW ANDCONCLUSION:
Clinical outcomes of gefitinib in patients with the STAT3 rs4796793C/C genotype depended on plasma concentrations of gefitinib. In addition to information regarding EGFR mutations, the STAT3 rs4796793C >G polymorphism and gefitinib C0 may be potential predictors of clinical outcomes after beginning of gefitinib therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Fator de Transcrição STAT3
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Gefitinibe
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Clin Pharm Ther
Ano de publicação:
2020
Tipo de documento:
Article