, Volume 11, Issue 3, pp 183–188 | Cite as

A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI)

  • Ken Kato
  • Kei Muro
  • Nobutoshi Ando
  • Tadashi Nishimaki
  • Atsushi Ohtsu
  • Kenjiro Aogi
  • Norio Aoyama
  • Kagami Nagai
  • Hoichi Kato
  • The Japan Esophageal Oncology Group of the Japan Clinical Oncology Group (JCOG)
Original Article



This phase II study evaluated the efficacy and toxicity of combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU) for metastatic esophageal squamous cell carcinoma.


Eligibility criteria included squamous cell carcinoma with organ metastasis, ECOG performance status (PS) 0–2, ≤ 75 years, measurable disease, and adequate organ function. Chemotherapy consisted of 5-FU (800 mg/m2/day) on days 1–5 and a 2-h infusion of nedaplatin (90 mg/m2) on day 1, repeated every 4 weeks. Therapy was continued until disease progression or intolerable adverse events. The primary end point was response rate. Secondary end points included overall survival, progression-free survival, and toxicities.


Forty-two patients (39 men, 3 women; median age 59 years; range 44–70 years) were enrolled. Twenty-one, 21, and 0 patients had PS 0, 1, and 2, respectively. 23, 6, 3, and 18 patients had a history of surgical resection, radiotherapy, adjuvant chemotherapy, and no therapy, respectively. Among the 38 eligible patients, 1 and 14 complete and partial responses were observed, respectively; the overall response rate was 39.5 % (90 % confidence interval: 26.1–54.1 %). The median survival time was 8.8 months. The one-year survival rate was 32.9 %. Grade 4 neutropenia and thrombocytopenia were observed in 7 and 2 % of 41 patients, respectively. Grade 3 nausea, diarrhea, and stomatitis were observed in 12, 2, and 2 %, respectively.


Combination therapy with nedaplatin and 5-FU is highly active and well tolerated in metastatic or recurrent esophageal squamous cell cancer and is therefore a chemotherapy option for esophageal squamous cell carcinoma.


Esophageal squamous cell carcinoma Chemotherapy 5-FU Nedaplatin 



We thank Ms. Makiko Shinogi and Ms. Hiromi Orita for collecting data. This study was supported by Grants-in-Aid for Cancer Research from the Ministry of Health, Labour, and Welfare of Japan.

Ethical Statement

This work conforms to the guidelines set forth in the Helsinki Declaration of 1975, as revised in 2000 (5), concerning Human and Animal Rights. We followed the policy concerning informed consent as shown on the following sites.

Conflict of interest

All authors declare that they have no conflicts of interest regarding this article.


  1. 1.
    Cancer Statistics in Japan 2007.Google Scholar
  2. 2.
    Iizuka T, Kakegawa T, Ide H, et al. Phase II evaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: A Japanese Esophageal Oncology Group Trial. Jpn J Clin Oncol. 1992;22:172–6.PubMedGoogle Scholar
  3. 3.
    Hayashi K, Ando N, Watanabe H, et al. Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407). Jpn J Clin Oncol. 2001;31:419–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Grünberger B, Raderer M, Schmidinger M, et al. Palliative chemotherapy for recurrent and metastatic esophageal cancer. Anticancer Res. 2007;27:2705–14.PubMedGoogle Scholar
  5. 5.
    Suzumura Y, Kato T, Ueda R, et al. Effect of treatment schedule on antitumor activity of glycolate-0,0′-diammineplatinum(II), a new platinum derivative: comparison with cis-diamminedichloroplatinum(II). Anticancer Res. 1989;9:1083–8.PubMedGoogle Scholar
  6. 6.
    Sasaki Y, Fukuda M, Morita M, et al. Prediction from creatinine clearance of thrombocytopenia and recommended dose in patients receiving (glycolato-O,O’)-diammine platinum (II) (NSC 375101D). Jpn J Cancer Res. 1990;81:196–200.PubMedCrossRefGoogle Scholar
  7. 7.
    Takeda Y, Kasai H, Uchida N, et al. Enhanced antitumor efficacy of nedaplatin with 5-fluorouracil against human squamous carcinoma xenografts. Anticancer Res. 1999;19(5B):4059–64.PubMedGoogle Scholar
  8. 8.
    Ota K, Wakui A, Majima H, et al. Phase I study of a new platinum complex 254-S, cis-diammine (glycolato)-platinum (II). Gan To Kagaku Ryoho. 1992;19:855–61.PubMedGoogle Scholar
  9. 9.
    Inuyama Y, Miyake H, Horiuchi M, et al. An early phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers. Gan To Kagaku Ryoho. 1992;19:863–9.PubMedGoogle Scholar
  10. 10.
    Furuse K, Fukuoka M, Kurita Y, et al. A phase II clinical study of cis-diammine glycolato platinum, 254-S, for primary lung cancer. Gan To Kagaku Ryoho. 1992;19:879–84.PubMedGoogle Scholar
  11. 11.
    Kato T, Nishimura H, Yakushiji M, et al. Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer. Gan To Kagaku Ryoho. 1992;19:695–701.PubMedGoogle Scholar
  12. 12.
    Taguchi T, Wakui A, Nabeya K, et al. A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group. Gan To Kagaku Ryoho. 1992;19:483–8.PubMedGoogle Scholar
  13. 13.
    Japanese Classification of Esophageal Cancer, 10th edn. Kanehara Shuppan, 2008.Google Scholar
  14. 14.
    Bleiberg H, Conroy T, Paillot B, et al. Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer. 1997;33:1216–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Ishikura S, Ohtsu A, Shirao K, et al. A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with T4 esophageal cancer: Japan Clinical Oncology Group trial (JCOG 9908). Esophagus. 2005;2:133–7.CrossRefGoogle Scholar
  16. 16.
    Sato Y, Takayama T, Sagawa T, et al. A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer. Cancer Chemother Pharmacol. 2006;58:570–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Conroy T, Yataghène Y, Etienne PL, et al. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010;103:1349–55.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Ajani JA, Ilson DH, Daugherty K, et al. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst. 1994;86:1086–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Kato K, Tahara M, Hironaka S, et al. A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. Cancer Chemother Pharmacol. 2011;67:1265–72.PubMedCrossRefGoogle Scholar
  20. 20.
    Ilson DH, Ajani J, Bhalla K, et al. Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol. 1998;16:1826–34.PubMedGoogle Scholar
  21. 21.
    Heath EI, Urba S, Marshall J, et al. Phase II trial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus. Investig New Drugs. 2002;20:95–9.CrossRefGoogle Scholar
  22. 22.
    Muro K, Hamaguchi T, Ohtsu A, et al. A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer. Ann Oncol. 2004;15:955–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009;20:1667–73.PubMedCrossRefGoogle Scholar
  24. 24.
    Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet. 2010;375:1030–47.PubMedCrossRefGoogle Scholar
  25. 25.
    Stella GM, Luisetti M, Inghilleri S, et al. Targeting EGFR in non-small-cell lung cancer: lessons, experiences, strategies. Respir Med. 2012;106:173–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Sudo T, Mimori K, Nagahara H, et al. Identification of EGFR mutations in esophageal cancer. Eur J Surg Oncol. 2007;33:44–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Licitra L, Mesia R, Rivera F. Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol. 2011;22:1078–87.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Caroli-Bosc FX, Van Laethem JL, Michel P, et al. A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) ± leucovorin and bi-weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon digestive carcinomas. Eur J Cancer. 2001;37(15):1828–32.PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Esophageal Society and Springer Japan 2014

Authors and Affiliations

  • Ken Kato
    • 1
  • Kei Muro
    • 1
    • 2
  • Nobutoshi Ando
    • 3
  • Tadashi Nishimaki
    • 4
  • Atsushi Ohtsu
    • 5
  • Kenjiro Aogi
    • 6
  • Norio Aoyama
    • 7
  • Kagami Nagai
    • 8
  • Hoichi Kato
    • 9
  • The Japan Esophageal Oncology Group of the Japan Clinical Oncology Group (JCOG)
  1. 1.Gastrointestinal Oncology DivisionNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Clinical OncologyAichi Cancer Center HospitalNagoyaJapan
  3. 3.Department of Surgery, Tokyo Dental CollegeIchikawa General HospitalIchikawaJapan
  4. 4.Department of SurgeryRyukyu University HospitalNishiharaJapan
  5. 5.Division of Gastrointestinal OncologyNational Cancer Center Hospital EastKashiwaJapan
  6. 6.Department of SurgeryNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  7. 7.Department of SurgeryKanagawa Cancer Center HospitalYokohamaJapan
  8. 8.Department of SurgeryTokyo Medical and Dental University School of MedicineTokyoJapan
  9. 9.Esophageal Surgery DivisionNational Cancer Center HospitalTokyoJapan

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