International Journal of Clinical Oncology

, Volume 11, Issue 6, pp 454–460 | Cite as

Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation

  • Takashi YoshiokaEmail author
  • Masato Sakayori
  • Shunsuke Kato
  • Natsuko Chiba
  • Shukichi Miyazaki
  • Kenji Nemoto
  • Hiroyuki Shibata
  • Hideki Shimodaira
  • Kazunori Ohtsuka
  • Yuichi Kakudo
  • Yuh Sakata
  • Chikashi Ishioka



Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation.


Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle.


Twelve patients were enrolled. At a docetaxel dose of 30 mg/m2 and a nedaplatin dose of 80 mg/m2, one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m2, respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission.


The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m2, respectively. This combination could be a potential second-line treatment for this target population.

Key words

Docetaxel Nedaplatin Esophageal cancer Definitive chemoradiation Dose escalation study 


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  1. 1.
    Muller, JM, Erasmi, H, Stelzner, M,  et al. 1990Surgical therapy of oesophageal carcinomaBr J Surg77845857PubMedGoogle Scholar
  2. 2.
    Ando, N, Ozawa, S, Kitagawa, Y,  et al. 2000Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive yearsAnn Surg232225232PubMedCrossRefGoogle Scholar
  3. 3.
    Herskovic, A, Martz, K, Al-Sarraf, M,  et al. 1992Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagusN Engl J Med32615931598PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper, JS, Guo, MD, Herskovic, A,  et al. 1999Chemoradiotherapy of locally advanced esophageal cancer. Long-term follow-up of a prospective randomized trial (RTOG 85-01)JAMA28116231627PubMedCrossRefGoogle Scholar
  5. 5.
    Ohtsu, A, Boku, N, Muro, K,  et al. 1999Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagusJ Clin Oncol1729152921PubMedGoogle Scholar
  6. 6.
    Chan, A, Wong, A 1999Is combined chemotherapy and radiation therapy equally effective as surgical resection in localized esophageal carcinoma?Int J Radiat Oncol Biol Phys45265270PubMedCrossRefGoogle Scholar
  7. 7.
    Hironaka, S, Ohtsu, A, Boku, N,  et al. 2003Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T2-3NanyM0 squamous cell carcinoma of the esophagusInt J Radiat Oncol Biol Phys57425433PubMedCrossRefGoogle Scholar
  8. 8.
    Walsh, TN, Noonan, N, Hollywood, D,  et al. 1996A comparison of multimodal therapy and surgery for esophageal adenocarcinomaN Engl J Med335462467PubMedCrossRefGoogle Scholar
  9. 9.
    Bosset, JF, Gignoux, M, Triboulet, JP,  et al. 1997Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagusN Engl J Med337161167PubMedCrossRefGoogle Scholar
  10. 10.
    Urba, SG, Orringer, MB, Turrisi, A,  et al. 2001Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinomaJ Clin Oncol19305313PubMedGoogle Scholar
  11. 11.
    Scanlon, KJ, Newman, EM, Lu, Y,  et al. 1986Biochemical basis for cisplatin and 5-fluorouracil synergism in human ovarian carcinoma cellsProc Natl Acad Sci USA8389238925PubMedCrossRefGoogle Scholar
  12. 12.
    Byfield, JE 1990Combined modality infusional chemotherapy with radiationLokich, JJ eds. Cancer Chemotherapy by infusion (2nd edn)PerceptaChicago521551Google Scholar
  13. 13.
    Araujo, CMM, Souhami, L, Gil, RA,  et al. 1991A randomized trial comparing radiation therapy versus concomitant radiation therapy and chemotherapy in carcinoma of the thoracic esophagusCancer6722582261PubMedCrossRefGoogle Scholar
  14. 14.
    Conroy, T, Etienne, PL, Adenis, A,  et al. 1996Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinomaJ Clin Oncol14164170PubMedGoogle Scholar
  15. 15.
    Lordick, F, von Schilling, C, Bernhard, H,  et al. 2003Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancerBr J Cancer89630633PubMedCrossRefGoogle Scholar
  16. 16.
    Muro, K, Hamaguchi, T, Ohtsu, A,  et al. 2004A phase II study of single-agent docetaxel in patients with metastatic esophageal cancerAnn Oncol15955959PubMedCrossRefGoogle Scholar
  17. 17.
    Ringel, I, Horwitz, SB 1991Studies with RP56976 (Taxotere): a semisynthetic analogue of TaxolJ Natl Cancer Inst83288291PubMedGoogle Scholar
  18. 18.
    Totani T, Aono K, Komura M (1986) Synthesis of (glycolato-o, o′) diammine platinum (II) and its related complexes. Chem Lett 429–432Google Scholar
  19. 19.
    Taguchi, T, Wakui, A, Nabeya, K,  et al. 1992A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancersJpn J Cancer Chemother19483488Google Scholar
  20. 20.
    Burstein, HJ, Manola, J, Younger, J,  et al. 2000Docetacel administered on a weekly basis for metastatic breast cancerJ Clin Oncol1812121219PubMedGoogle Scholar
  21. 21.
    Fukuda, H, Saijyo, N 2001National Cancer Institute – Common Toxicity Criteria (NCI-CTC version 2.0, April 30, 1999) – The second version translated into Japanese by Japan Clinical Oncology GroupJpn J Cancer Chemother2819932027Google Scholar
  22. 22.
    Therasse, P, Arbuck, SG, Eisenhauer, EA,  et al. 2000New guidlines to evaluate the response to treatment in solid tumorsJ Natl Cancer Inst92205216PubMedCrossRefGoogle Scholar
  23. 23.
    Japanese Society for Esophageal Diseases1992Guidelines for the clinical and pathologic studies on carcinoma of the esophagus (8th edn)Kanehara SyuppanTokyoGoogle Scholar
  24. 24.
    Yoshioka, T, Gamoh, M, Shineha, R,  et al. 1999A new combination chemotherapy with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for advanced esophageal cancersInternal Medicine38844848PubMedGoogle Scholar
  25. 25.
    Muro, K, Shirao, K, Shimada, Y,  et al. 1999A phase I-II study of nedaplatin and 5-fluorouracil in patients with advanced esophageal cancerProc ASCO18258aGoogle Scholar
  26. 26.
    Shibata, S, Kawasaki, H, Nakai, M,  et al. 2002Chemoradiotherapy using platinum analogs/5-FU for advanced esophageal cancerJpn J Cancer Chemother2922092212Google Scholar
  27. 27.
    Nakamura, T, Ide, H, Eguchi, R,  et al. 2003Nedaplatin and 5-fluorouracil combined with radiotherapy for advanced esophageal cancerJpn J Chemoter30803807Google Scholar
  28. 28.
    Nemoto, K, Matsushita, H, Ogawa, Y,  et al. 2003Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for untreated and recurrent esophageal cancerAm J Clin Oncol264649PubMedCrossRefGoogle Scholar
  29. 29.
    Kato, H, Fukuchi, M, Manda, R,  et al. 2003Efficacy and toxicity of nedaplatin and 5-FU with radiation for advanced esophageal carcinomasAnticancer Res2334933498PubMedGoogle Scholar
  30. 30.
    Kobayashi, H, Takemura, Y, Miyachi, H, Ogawa, T 1991Antitumor activities of new platinum compounds, DWA2114R, NK121 and 254-S, against human leukemia cells sensitive or resistant to cisplatinInvest New Drugs9313319PubMedCrossRefGoogle Scholar
  31. 31.
    Fukuda, M, Ohe, Y, Kanazawa, F,  et al. 1995Evaluation of novel platinum complexes, inhibitors of topoisomerase I and II in non-small cell lung cancer (NSCLC) sublines resistant to cisplatinAnticancer Res15393398PubMedGoogle Scholar
  32. 32.
    Alberts, DS, Fanta, PT, Running, KL,  et al. 1997In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancersCancer Chemother Pharmacol39493497PubMedCrossRefGoogle Scholar
  33. 33.
    Monk, BJ, Alberts, DS, Burger, RA,  et al. 1998In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancersGynecol Oncol71308312PubMedCrossRefGoogle Scholar

Copyright information

© The Japan Society of Clinical Oncology 2006

Authors and Affiliations

  • Takashi Yoshioka
    • 1
    Email author
  • Masato Sakayori
    • 1
  • Shunsuke Kato
    • 1
  • Natsuko Chiba
    • 1
  • Shukichi Miyazaki
    • 2
  • Kenji Nemoto
    • 3
  • Hiroyuki Shibata
    • 1
  • Hideki Shimodaira
    • 1
  • Kazunori Ohtsuka
    • 1
  • Yuichi Kakudo
    • 1
  • Yuh Sakata
    • 4
  • Chikashi Ishioka
    • 1
  1. 1.Department of Clinical Oncology, Institute of DevelopmentAging and Cancer, Tohoku UniversitySendaiJapan
  2. 2.Division of Advanced Surgery and TechnologyTohoku University Graduate School of MedicineSendaiJapan
  3. 3.Department of Radiation OncologyTohoku University Graduate School of MedicineSendaiJapan
  4. 4.Misawa City HospitalMisawaJapan

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