Randomized phase III trial of adjuvant chemotherapy with S-1 after curative treatment in patients with squamous-cell carcinoma of the head and neck (ACTS-HNC)

PLoS One. 2015 Feb 11;10(2):e0116965. doi: 10.1371/journal.pone.0116965. eCollection 2015.

Abstract

Background: We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN).

Patients and methods: Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety.

Results: A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group.

Conclusions: Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN.

Trial registration: ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Chemotherapy, Adjuvant
  • Drug Combinations
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Safety
  • Squamous Cell Carcinoma of Head and Neck
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Treatment Outcome

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid

Associated data

  • ClinicalTrials.gov/NCT00336947

Grants and funding

This study was sponsored by the ‘Foundation for Biomedical Research and Innovation, Translational Research Informatics Center,’ with funding from Taiho Pharmaceutical Co., Ltd., Japan (http://www.taiho.co.jp/english/) under the study contract. The funding source of the study participated in study design, but had no role in data collection, data management, data analysis, and data interpretation. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.