| Title |
A phase I/II study of S-1 with sorafenib in patients with advanced hepatocellular carcinoma
|
|---|---|
| Published in |
Investigational New Drugs, March 2014
|
| DOI | 10.1007/s10637-014-0077-6 |
| Pubmed ID | |
| Authors |
Yoshihiko Ooka, Tetsuhiro Chiba, Sadahisa Ogasawara, Kuniaki Arai, Eiichiro Suzuki, Akinobu Tawada, Tatsuya Yamashita, Fumihiko Kanai, Shuichi Kaneko, Osamu Yokosuka |
| 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 5 | 21% |
| Researcher | 4 | 17% |
| Student > Postgraduate | 3 | 13% |
| Student > Ph. D. Student | 2 | 8% |
| Student > Master | 2 | 8% |
| Other | 5 | 21% |
| Unknown | 3 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 14 | 58% |
| Biochemistry, Genetics and Molecular Biology | 4 | 17% |
| Agricultural and Biological Sciences | 1 | 4% |
| Unknown | 5 | 21% |
Attention Score in Context
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#15,303,385
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Outputs of similar age from Investigational New Drugs
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