A phase I/II study of S-1 with sorafenib in patients with advanced hepatocellular carcinoma.
Invest New Drugs
; 32(4): 723-8, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24599799
ABSTRACT
BACKGROUND:
Sorafenib is the sole molecular-targeted agent showing a survival benefit in patients with advanced hepatocellular carcinoma (HCC). We evaluated the tolerability and effectiveness of a combination of S-1 with sorafenib in patients with advanced HCC.METHODS:
S-1 was administered during days 1-14 and sorafenib was administered every day. This treatment was repeated every 21 days. In phase I, we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). The dose of each drug was planned as follows cohort 1 S-1 48 mg/m(2)/day and sorafenib 400 mg/day, cohort 2a S-1 48 mg/m(2)/day and sorafenib 800 mg/day, cohort 2b S-1 64 mg/m(2)/day and sorafenib 400 mg/day, cohort 3 S-1 64 mg/m(2)/day and sorafenib 800 mg/day, and cohort 4 S-1 80 mg/m(2)/day and sorafenib 800 mg/day. In phase II, the patients were treated at the MTD to evaluate safety and efficacy.RESULTS:
Nineteen patients were enrolled in phase I. One of the six patients in cohort 1 and one of the six patients in cohort 3 experienced DLT. None of the three patients in cohort 2a experienced DLT and three of the four patients in cohort 4 experienced DLT. Therefore, cohort 3 was considered the MTD. Subsequently, 26 patients were enrolled in phase II. The most common grade 3/4 toxicities were an increase of aspartate aminotransferase (38.5 %), thrombocytopenia (23.1 %), neutropenia (19.2 %), hyperbilirubinemia (15.4 %), an increase of alanine aminotransferase (15.4 %), hyponatremia (11.5 %), rash (11.5 %), and hypophosphatemia (11.5 %). Sudden death occurred in one patient (3.8 %). A patient (3.8 %) had a partial response, 15 (57.7 %) had stable disease, and 10 (38.5 %) had progressive disease. The median times to progression and overall survival were 2.4 and 10.5 months, respectively.CONCLUSION:
The MTD of S-1 and sorafenib in patients with advanced HCC was 64 mg/m(2)/day and 800 mg/day, respectively. This dose/regimen demonstrated substantial clinical activity among patients with advanced HCC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Tipo de estudo:
Observational_studies
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Risk_factors_studies
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:
Invest New Drugs
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Japão