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)

<div><p>Background</p><p>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).</p><p>Patients and Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial Registration</p><p><a href="http://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a> NCT00336947 <a href="http://clinicaltrials.gov/show/NCT00336947" target="_blank">http://clinicaltrials.gov/show/NCT00336947</a></p></div

Comparison of clinical characteristics between the chemoradiotherapy group and the other therapy group.

<p>Comparison of clinical characteristics between the chemoradiotherapy group and the other therapy group.</p

Treatment completion rates.

<p>Treatment completion rates.</p

Definition of definitive treatment.

<p>Abbreviations: RT, radiotherapy. CRT, chemoradiotherapy.</p

Cumulative rates of locoregional recurrence (A) and distant metastasis (B).

<p>(A) One patient with secondary cancer before locoregional recurrence was censored. (B) One patient with secondary cancer before distant metastasis was censored.</p

Patient characteristics.

<p>Patient characteristics.</p

Overall survival in the CRT group.

<p>(A) OS derived from Kaplan–Meier curves. (B) HR and corresponding CI were calculated using Cox proportional hazard model. <i>P</i> values were calculated based on stratified log-rank test. Abbreviations: CI, confidence interval. HR, hazard ratio. OS, overall survival.</p

Distant metastasis-free survival in the CRT group.

<p>(A) DMFS derived from Kaplan–Meier curves. (B) HR and corresponding CI were calculated using Cox proportional hazard model. P values were calculated based on stratified log-rank test. Abbreviations: CI, confidence interval; HR, hazard ratio; DMFS, distant metastasis-free survival.</p

Subsets by curative treatment before random allocation.

<p>Abbreviations: ACTS-HNC, Adjuvant chemo<u>t</u>herapy with S-1 after curative treatment in patients with Head and Neck Cancer. CRT, chemoradiotherapy.</p

Post- locoregional relapse survival in the CRT group.

<p>(A) Post-LRRS derived from Kaplan–Meier curves. (B) HR and corresponding CI were calculated using Cox proportional hazard model. <i>P</i> values were calculated based on stratified log-rank test. Abbreviations: CI, confidence interval; HR, hazard ratio; post-LRRS, post-locoregional relapse-free survival.</p