P-0135 - Phase I trial of 5-FU, Docetaxel and Nedaplatin combination therapy for metastatic esophageal cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Presenter Shinichi Nishina
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors S. Nishina1, S. Ueda2, Y. Nonagase1, T. Okabe1, H. Kawakami1, T. Sakiyama1, K. Nakagawa1
  • 1Kinki University School of Medicine, Osakasayama/JP
  • 2Nara Hospital Kinki University School of Medicine, Ikoma/JP



The optimal chemotherapy for the metastatic esophageal cancer has not been established. Although a combination chemotherapy of 5-FU and cisplatin is commonly used as the 1st line chemotherapy for the patients with metastatic or recurrent esophageal cancer, the prognosis of such patients remains poor with the aggressiveness of the tumor and the weakness of the patients, requiring more effective and safe treatments. In recent years, a new chemotherapeutic regimen consisting of 5-FU, docetaxel and cisplatin has been performed in esophageal cancer. This regimen was more effective but toxic for patients with poor condition. Nedaplatin, a cisplatin analog, has been developed to decrease the toxicities induced by cisplatin, such as nephrotoxicity and gastrointestinal toxicity. The aim of this dose-escalating phase I study was to determine the recommend dose of 5-FU, docetaxel and nedaplatin (UDON) combination therapy and evaluate the safety and the efficacy of this therapy in patients with untreated metastatic esophageal cancer.


Eligible patients had histological confirmed metastatic or recurrent esophageal cancer, Eastern Cooperative Oncology Group performance status 0 or 1 and adequate organ function. Patients were administered 5-FU on days1-5, docetaxel on days 1 and 15, and nedaplatin on day 1. Cycles were repeated every 4 weeks. The dose levels of 5-FU/docetaxel/nedaplatin were defined as follows: level 1: 800/30/80 mg/ m2, level 2: 800/30/90 mg/ m2, level 3: 800/35/90 mg/ m2, respectively. Toxicity was examined by the CTCAE version 4.0.


A total of nine patients (male/female 8/1, mean age 69 years) were enrolled in this study. All patients were diagnosed with squamous cell carcinoma and had metastatic and evaluable lesions in initially visit. Treatment has been carried out two or more cycles in all cases. The dose limiting toxicity such as grade 4 neutropenia lasting for 5 days and grade 4 thrombocytopenia was not occurred in any levels. Grade 3 or 4 hematological toxicities were as follows: leukopenia in 3 patients (33%), neutropenia in 5 patients (56%). None of the patients developed a febrile neutropenic infection. The grade 3 or 4 non-hematological toxicities were not observed. Response status was as follows: one CR case, six PR cases, one SD case and no PD case. The overall response rate was 87.5%.


The recommended dose of this UDON regimen was determined that 5-FU was 800mg/ m2 on day 1-5, docetaxel was 35mg/m2 on days 1 and 15, nedaplatin was 90mg/ m2 on day 1. This UDON regimen was tolerable and highly active. We are now conducting a Phase II study.