Cancer Chemotherapy and Pharmacology (2018) 81:565–572
Long-term results of S-1 plus cisplatin with concurrent thoracic
radiotherapy for locally advanced non-small-cell lung cancer
· Kiyotaka Yoh
· Seisuke Nagase
· Kaoru Kubota
· Hironobu Ohmatsu
· Seiji Niho
· Tetsuo Akimoto
· Yuichiro Ohe
· Koichi Goto
Received: 25 August 2017 / Accepted: 26 January 2018 / Published online: 31 January 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose The purpose of this phase I/II study was to evaluate the feasibility and eﬃcacy of S-1 plus cisplatin at the recom-
mended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).
Methods Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m
on day 8 plus
oral S-1 at a dosage of 40 mg/m
twice per day for two diﬀerent treatment schedules for up to 4 cycles. Patients also concur-
rently received 60 Gy of thoracic radiation in 30 fractions. The primary endpoint of the phase II study was the proportion
of patients who survived for more than 2 years.
Results Between August 2005 and October 2010, a total of 45 patients were enrolled in this phase I/II study; their long-term
survival was then followed for a median period of 5.8 years. Nineteen of the 39 patients in the phase II study survived for
more than 2 years and met the primary endpoint of the study. The median overall survival period was 24.9 months [95%
conﬁdence interval (CI) 17.4–74.5 months], and the 2- and 5-year overall survival rates were 51.0 and 43.0%, respectively.
The response rate was 85%, and the median progression-free survival period was 13.8 months (95% CI 9.5–27.1 months).
Hematological toxicity was mild. Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5%, respectively.
Conclusion Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival
outcomes and an acceptable safety proﬁle for LA-NSCLC.
Keywords Concurrent chemoradiotherapy · S-1 · Cisplatin · Non-small cell lung cancer
Lung cancer is the leading cause of cancer-related mortality
worldwide . The standard treatment for locally advanced
non-small cell lung cancer (LA-NSCLC) is chemoradio-
therapy (CRT) . Even with this combined modality treat-
ment, the majority of patients with unresectable stage III
NSCLC experience recurrence, with a 5-year survival rate
of approximately 20% [3–6]. Therefore, outcomes remain
far from satisfactory. Previously reported studies comparing
concurrent versus sequential chemoradiotherapy showed a
survival beneﬁt from concurrent treatment. Concurrent CRT
is preferred, but serious adverse events, such as myelosup-
pression, esophagitis, or pneumonitis, are a major problem
with this combined modality treatment [7, 8]. Consequently,
a new and less toxic therapy that can control both locore-
gional and micrometastatic disease is necessary.
S-1 (Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) is an
oral antitumor agent designed to enhance antitumor activity
and to reduce gastrointestinal toxicity . A randomized
phase III study of S-1 plus cisplatin versus docetaxel plus
cisplatin in Japanese patients with advanced NSCLC showed
that S-1 plus cisplatin was not inferior to docetaxel plus cis-
platin . The schedule of S-1 plus cisplatin was S-1 on
days 1–21 plus cisplatin on day 8 every 4–5 weeks. Fur-
thermore, a statistically signiﬁcant lower rate of toxicity,
including febrile neutropenia, neutropenia, and infection,
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0028 0-018-3530-y) contains
supplementary material, which is available to authorized users.
* Kiyotaka Yoh
Department of Thoracic Oncology, National Cancer
Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa,
Chiba 277-8577, Japan
Department of Radiation Oncology, National Cancer Center
Hospital East, Kashiwa, Japan