A phase II trial of S-1 and oxaliplatin in patients with advanced hepatocellular carcinoma

Abstract

Background: Oxaliplatin is a platinum derivative that has shown efficacy in advanced hepatocellular carcinoma. S-1 is an oral fluoropyrimidine that has substituted for 5-fluorouracil in many cancers. This was a multicenter, open-label, single-arm phase II trial that evaluated the efficacy of S-1 and oxaliplatin (SOX) in advanced hepatocellular carcinoma. All patients included in the present study were systemic treatment-naïve. Prior treatment with sorafenib was allowed, but other treatments were not.

Methods: Patients received S-1 (40 mg/m2 twice daily from day 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. The primary end point was time to progression (TTP). Secondary end points included progression-free survival, overall survival (OS), response rate, and safety profile.

Results: Thirty six patients with advanced hepatocellular carcinoma were included in this study. The median TTP was 3.0 months (95% confidence interval (CI), 0.75-5.25), and the median OS was 10.3 months (95% CI, 6.4-14.3). Bone metastasis was associated with poorer TTP and OS. The efficacy of SOX was unaffected by prior sorafenib or locoregional therapy. The objective response rate was 13.9%. No grade 4 toxicity or death from adverse events occurred. The most common grade 3 toxicities were neutropenia (13.9%), thrombocytopenia (13.9%), and diarrhea (8.3%).

Conclusions: Although this trial did not meet its primary end point, the SOX regimen showed comparable efficacy and safety to the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen. As the SOX regimen is easier for patients, SOX may be a reasonable substitute for FOLFOX in hepatocellular carcinoma.

Trial registration: Clinicaltrials.gov NCT01429961 . Registered 7 September 2011.

Keywords: Chemotherapy; Hepatocellular carcinoma; Oxaliplatin; Phase II; S-1.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was reviewed and approved by the institutional review board of Seoul National University Hospital, Seoul, Korea [H-1010-054-336]. This study was carried out in accordance with the recommendations of the Declaration of Helsinki for biomedical research involving human subjects and the Guidelines for Good Clinical Practice (ClinicalTrial.gov Identifier: NCT01429961). Written informed consent was obtained from each patient before enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

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Figures

Fig. 1

Kaplan–Meier survival curve for time to progression

Fig. 2

Kaplan–Meier survival curve for overall survival

Fig. 3

Kaplan–Meier curves of TTP and OS according to the presence of bone metastasis. Abbreviations: TTP, time to progression; OS, overall survival