Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for locally advanced esophageal squamous cell carcinoma

  • Ken SasakiEmail author
  • Yasuto Uchikado
  • Itaru Omoto
  • Takaaki Arigami
  • Yusaku Osako
  • Masahiro Noda
  • Hiroshi Okumura
  • Kosei Maemura
  • Ryutaro Higashi
  • Takashi Yoshiura
  • Shoji Natsugoe
Original Article



To further improve the prognosis of esophageal cancer patients, it is necessary to investigate new treatment strategies. The purposes of this study were to retrospectively assess the safety and efficacy of neoadjuvant chemoradiotherapy (CRT) with docetaxel/cisplatin/5-fluorouracil (DCF) (DCF-RT) in patients with thoracic esophageal squamous cell carcinoma (ESCC).


We reviewed 30 thoracic ESCC patients who underwent neoadjuvant DCF-RT followed by esophagectomy, and evaluated the safety and efficacy of DCF-RT. DCF-RT consisted of 40 Gy radiation with two courses of intravenous DCF (docetaxel, 30 mg/m2/day, day 1; cisplatin, 7 mg/m2/day, day 1; 5-FU, 350 mg/m2/day, days 1–5 and days 8–12) repeated every 2 weeks. Esophagectomy was scheduled 8–10 weeks after completion of DCF-RT.


Twenty-nine of thirty patients completed radiotherapy; however, 27 of 30 patients required dose reduction of the second cycle of DCF. Complete response (CR), partial response, and stable disease were observed in 7, 11, and 10 patients, respectively. The number of lymph node metastases after DCF-RT was significantly lower than that before DCF-RT (P < 0.0001). Among the 30 patients, pathological CR (pCR) in the primary tumor was observed in 17 patients, and pCRs in both the primary tumor and lymph nodes were observed in 14 patients. The 3-year overall survival rate was 62.2%, and that of patients who experienced pCR was 84%.


Neoadjuvant DCF-RT was tolerable and yielded a high pCR rate in ESCC. Therefore, neoadjuvant DCF-RT may confer a survival benefit and may be a candidate neoadjuvant therapy regimen for patients with locally advanced thoracic ESCC.


Esophageal squamous cell carcinoma Neoadjuvant chemoradiotherapy Docetaxel Cisplatin 5-Fluorouracil 



This work was supported by JSPS KAKENHI Grant number 17K10706.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


  1. 1.
    Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19(1):68–74CrossRefGoogle Scholar
  2. 2.
    Hara H, Tahara M, Daiko H, Kato K, Igaki H, Kadowaki S, Tanaka Y, Hamamoto Y, Matsushita H, Nagase M (2013) Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma. Cancer Sci 104(11):1455–1460CrossRefGoogle Scholar
  3. 3.
    Yamasaki M, Yasuda T, Yano M, Hirao M, Kobayashi K, Fujitani K, Tamura S, Kimura Y, Miyata H, Motoori M (2017) Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003). Ann Oncol 28(1):116–120Google Scholar
  4. 4.
    Higuchi K, Komori S, Tanabe S, Katada C, Azuma M, Ishiyama H, Sasaki T, Ishido K, Katada N, Hayakawa K (2014) Definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) in advanced esophageal cancer: a phase 2 trial (KDOG 0501-P2). Int J Radiat Oncol Biol Phys 89(4):872–879CrossRefGoogle Scholar
  5. 5.
    Okamoto H, Taniyama Y, Sakurai T, Heishi T, Teshima J, Sato C, Maruyama S, Ito K, Onodera Y, Konno-Kumagai T (2018) Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer. Esophagus 15(4):1–5CrossRefGoogle Scholar
  6. 6.
    van Hagen P, Hulshof M, Van Lanschot J, Steyerberg E, Henegouwen MvB, Wijnhoven B, Richel D, Nieuwenhuijzen G, Hospers G, Bonenkamp J (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084CrossRefGoogle Scholar
  7. 7.
    Nakamura K, Kato K, Igaki H, Ito Y, Mizusawa J, Ando N, Udagawa H, Tsubosa Y, Daiko H, Hironaka S (2013) Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol 43(7):752–755CrossRefGoogle Scholar
  8. 8.
    Health UDo, Services H (2009) Common terminology criteria for adverse events (CTCAE) version 4.0. National Institutes of Health, National Cancer Institute 4 (03)Google Scholar
  9. 9.
    Japan Esophageal Society (2017) Japanese Classification of Esophageal Cancer, 11th edn: part II and III. Esophagus 14(1):37–65. CrossRefGoogle Scholar
  10. 10.
    Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibañes E, Pekolj J, Slankamenac K, Bassi C (2009) The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196CrossRefGoogle Scholar
  11. 11.
    Shapiro J, Van Lanschot JJB, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098CrossRefGoogle Scholar
  12. 12.
    Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen A-B, Friesland S, Hatlevoll I, Glenjen N, Lind P, Tsai J (2016) A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol 27(4):660–667CrossRefGoogle Scholar
  13. 13.
    Pasini F, de Manzoni G, Zanoni A, Grandinetti A, Capirci C, Pavarana M, Tomezzoli A, Rubello D, Cordiano C (2013) Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long-lasting pathological complete response. Cancer 119(5):939–945CrossRefGoogle Scholar
  14. 14.
    Spigel DR, Greco FA, Meluch AA, Lane CM, Farley C, Gray JR, Clark BL, Burris HA III, Hainsworth JD (2010) Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol 28(13):2213–2219CrossRefGoogle Scholar
  15. 15.
    Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, Marcovalerio M, Shah N, Kelley S, Karl R (2010) Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 17(4):1159–1167CrossRefGoogle Scholar
  16. 16.
    Donahue JM, Nichols FC, Li Z, Schomas DA, Allen MS, Cassivi SD, Jatoi A, Miller RC, Wigle DA, Shen KR (2009) Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 87(2):392–399CrossRefGoogle Scholar
  17. 17.
    Tsang J, Tong D, Lam K, Law B, Wong I, Chan D, Chan F, Kwong D, Law S (2017) Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer. Dis Esophagus 30(9):1–8CrossRefGoogle Scholar
  18. 18.
    van der Werf L, Dikken J, van der Willik E, van Berge Henegouwen M, Nieuwenhuijzen G, Wijnhoven B, Bosscha K, van Grieken N, Hartgrink H, van Hillegersberg R (2018) Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: a nationwide study. Eur J Cancer 91:76–85CrossRefGoogle Scholar
  19. 19.
    Shapiro J, van Hagen P, Lingsma HF, Wijnhoven BP, Biermann K, ten Kate FJ, Steyerberg EW, van der Gaast A, van Lanschot JJB, Group CS (2014) Prolonged time to surgery after neoadjuvant chemoradiotherapy increases histopathological response without affecting survival in patients with esophageal or junctional cancer. Ann Surg 260(5):807–814CrossRefGoogle Scholar
  20. 20.
    Shaikh T, Ruth K, Scott WJ, Burtness BA, Cohen SJ, Konski AA, Cooper HS, Astsaturov I, Meyer JE (2015) Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer. Ann Thorac Surg 99(1):270–276CrossRefGoogle Scholar
  21. 21.
    Tessier W, Gronnier C, Messager M, Hec F, Mirabel X, Robb WB, Piessen G, Mariette C (2014) Does timing of surgical procedure after neoadjuvant chemoradiation affect outcomes in esophageal cancer? Ann Thorac Surg 97(4):1181–1189CrossRefGoogle Scholar
  22. 22.
    Lin G, Han S-Y, Xu Y-P, Mao W-M (2017) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer: a meta-analysis of published studies. Dis Esophagus 30(7):1–8Google Scholar
  23. 23.
    Kataoka K, Takeuchi H, Mizusawa J, Igaki H, Ozawa S, Abe T, Nakamura K, Kato K, Ando N, Kitagawa Y (2017) Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer: exploratory analysis of JCOG9907. Ann Surg 265(6):1152–1157CrossRefGoogle Scholar
  24. 24.
    Shridhar R, Takahashi C, Huston J, Doepker MP, Meredith KL (2018) Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer. J Gastrointest Oncol 9:894CrossRefGoogle Scholar
  25. 25.
    Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R (2008) Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26(7):1086CrossRefGoogle Scholar
  26. 26.
    Markar SR, Arya S, Karthikesalingam A, Hanna GB (2013) Technical factors that affect anastomotic integrity following esophagectomy: systematic review and meta-analysis. Ann Surg Oncol 20(13):4274–4281CrossRefGoogle Scholar
  27. 27.
    Kassis ES, Kosinski AS, Ross P Jr, Koppes KE, Donahue JM, Daniel VC (2013) Predictors of anastomotic leak after esophagectomy: an analysis of the society of thoracic surgeons general thoracic database. Ann Thorac Surg 96(6):1919–1926CrossRefGoogle Scholar
  28. 28.
    Hironaka S, Tsubosa Y, Mizusawa J, Kii T, Kato K, Tsushima T, Chin K, Tomori A, Okuno T, Taniki T (2014) Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG 0807). Cancer Sci 105(9):1189–1195CrossRefGoogle Scholar
  29. 29.
    Natsugoe S, Okumura H, Matsumoto M, Uchikado Y, Setoyama T, Yokomakura N, Ishigami S, Owaki T, Aikou T (2006) Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution. Dis Esophagus 19(6):468–472CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ken Sasaki
    • 1
    Email author return OK on get
  • Yasuto Uchikado
    • 1
  • Itaru Omoto
    • 1
  • Takaaki Arigami
    • 1
  • Yusaku Osako
    • 1
  • Masahiro Noda
    • 1
  • Hiroshi Okumura
    • 1
  • Kosei Maemura
    • 1
  • Ryutaro Higashi
    • 2
  • Takashi Yoshiura
    • 2
  • Shoji Natsugoe
    • 1
  1. 1.Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshimaJapan
  2. 2.Department of Radiology, Graduate School of Medical and Dental SciencesKagoshima UniversityKagoshimaJapan

Personalised recommendations