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Clinical Trial
. 2018 Jun 8;13(6):e0198391.
doi: 10.1371/journal.pone.0198391. eCollection 2018.

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study

Akira Kubota  1 , Eiji Nakatani  2 , Kiyoaki Tsukahara  3 , Yasuhisa Hasegawa  4 , Hideki Takemura  5 , Tomonori Terada  6 , Takahide Taguchi  7 , Kunihiko Nagahara  8 , Hiroaki Nakatani  9 , Kunitoshi Yoshino  10 , Yuichiro Higaki  11 , Shigemichi Iwae  12 , Takeshi Beppu  13 , Yutaka Hanamure  14 , Kichinobu Tomita  15 , Naoyuki Kohno  16 , Kazuyoshi Kawabata  17 , Satoshi Teramukai  18 , Masato Fujii  19 ; ACTS-HNC Study Group
Affiliations
Clinical Trial

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study

Akira Kubota et al. PLoS One. .

Abstract

Background: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study.

Methods: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival.

Results: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT.

Conclusion: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

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Conflict of interest statement

A. Kubota has received honoraria from AstraZeneca, Otsuka Pharmaceutical, and Taiho Pharmaceutical; and research funding from Taiho. K. Tsukahara has received honoraria from Covidien Japan, FUJIFILM Medical, Johnson & Johnson, KYORIN Pharmaceutical, Kyowa Hakko Kirin, Merck Serono, Mitsubishi Tanabe Pharma Corporation, and Sanofi. T. Terada has received honoraria from GlaxoSmithKline, KYORIN, Merck Serono, and Ono Pharmaceutical. T. Taguchi has received an honorarium from Taiho. K. Nagahara has received honoraria from Kowa Pharmaceutical and Taisho Toyama Pharmaceutical. S. Iwae has received honoraria from Ono and Otsuka. K. Tomita has received an honorarium from KYORIN. S. Teramukai has received consulting fees from Bristol-Myers Squibb, Daiichi Sankyo, Sanofi, Sysmex Corporation, and Taiho; and research funding from Daiichi Sankyo. M. Fujii has received honoraria from Bristol-Myers Squibb, Merck Serono, and Taiho; and research funding from Taiho. The other authors have declared no conflicts of interest. We confirm that our potential interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Subsets by curative treatment before random allocation.
Abbreviations: ACTS-HNC, Adjuvant chemotherapy with S-1 after curative treatment in patients with Head and Neck Cancer. CRT, chemoradiotherapy.
Fig 2
Fig 2. Forest plot for subset analysis.
Abbreviations: CI, confidence interval. DFS, disease-free survival. DMFS, distant metastasis-free survival. LRRFS, locoregional relapse-free survival. OS, overall survival. post-LRRS, post-locoregional relapse-free survival. UFT, tegafur/uracil.
Fig 3
Fig 3. Overall survival in the CRT group.
(A) OS 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. OS, overall survival.
Fig 4
Fig 4. Distant metastasis-free survival in the CRT group.
(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.
Fig 5
Fig 5. Post- locoregional relapse survival in the CRT group.
(A) Post-LRRS 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; post-LRRS, post-locoregional relapse-free survival.
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