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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지
Article de En | WPRIM | ID: wpr-763143
Bibliothèque responsable: WPRO
ABSTRACT
PURPOSE: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. RESULTS: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). CONCLUSION: OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.
Sujet(s)
Mots clés
Texte intégral: 1 Indice: WPRIM Sujet Principal: Thrombopénie / Marqueurs biologiques / Études de cohortes / Carcinome hépatocellulaire / Survie sans rechute / Dose maximale tolérée / Sensation vertigineuse / Facteur de transcription STAT-3 / Fatigue Type d'étude: Clinical_trials / Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limites du sujet: Humans langue: En Texte intégral: Cancer Research and Treatment Année: 2019 Type: Article
Texte intégral: 1 Indice: WPRIM Sujet Principal: Thrombopénie / Marqueurs biologiques / Études de cohortes / Carcinome hépatocellulaire / Survie sans rechute / Dose maximale tolérée / Sensation vertigineuse / Facteur de transcription STAT-3 / Fatigue Type d'étude: Clinical_trials / Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limites du sujet: Humans langue: En Texte intégral: Cancer Research and Treatment Année: 2019 Type: Article