Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma

  • Shinichiro KinaEmail author
  • Toshiyuki Nakasone
  • Takao Kinjo
  • Fumikazu Nimura
  • Nao Sunagawa
  • Akira Arasaki
Original Article



Our aim was to investigate the disease-free survival in patients with tongue squamous cell carcinoma receiving metronomic neoadjuvant chemotherapy with 5-fluorouracil prodrugs (UFT or S-1) plus bleomycin compared with those who had up-front surgery retrospectively.


In this retrospective study, 108 patients with stages I to II tongue squamous cell carcinoma who had undergone surgery were divided into the “surgery group” or “neoadjuvant chemotherapy group.”


A total of 41 patients received up-front surgery; 67 received metronomic neoadjuvant chemotherapy with UFT plus bleomycin (39) or S-1 plus bleomycin (28). The rate of disease-free survival was the primary outcome measure. Neoadjuvant 5-fluorouracil prodrugs did not correlate higher with improved disease-free survival than up-front surgery (72 and 54%, respectively; hazard ratio for recurrence or death, 0.54; 95% confidence interval [CI], 0.28 to 1.03; P = 0.06). Patients who received S-1 were more likely than those who received UFT to have pathological complete response (46% vs. 15%; P = 0.007). Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery (79% vs. 54%; hazard ratio, 0.41; 95% CI, 0.15 to 0.98; P = 0.04). However, neoadjuvant UFT did not improve disease-free survival as compared with up-front surgery (67% vs. 54%, respectively; hazard ratio, 0.66; 95% CI, 0.31 to 1.33; P = 0.24).


Neoadjuvant S-1 chemotherapy, as compared with up-front surgery, significantly improved disease-free survival among patients with tongue squamous cell carcinoma.

Clinical relevance

A choice of drugs before neoadjuvant metronomic chemotherapy is needed.


Metronomic S-1 Neoadjuvant Chemotherapy Tongue squamous cell carcinoma 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed were in accordance with the ethics committee at the University of the Ryukyus (No. 772), and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

We treated the patients at the Department of Oral and Maxillofacial Surgery, and all patients provided written informed consent.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Oral and Maxillofacial Functional Rehabilitation, Graduate School of MedicineUniversity of the RyukyusNishiharaJapan
  2. 2.Department of Molecular Pharmacology and OncologyGunma UniversityMaebashiJapan
  3. 3.Department of Oral and Maxillofacial SurgeryUniversity Hospital of the RyukyusNishiharaJapan
  4. 4.Division of Morphological Pathology, Department of Basic Laboratory Sciences, School of Health SciencesUniversity of the RyukyusNishiharaJapan
  5. 5.Department of Oral and Maxillofacial SurgeryOkinawa Red Cross HospitalNahaJapan

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