Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)

Cancer Sci. 2015 Apr;106(4):407-12. doi: 10.1111/cas.12622. Epub 2015 Mar 9.


Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

Keywords: Chemoradiotherapy; esophageal squamous cell carcinoma; randomized trial; survival; toxicity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Cisplatin / therapeutic use
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / radiotherapy
  • Esophageal Neoplasms / therapy*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Treatment Outcome


  • Antineoplastic Agents
  • Cisplatin
  • Fluorouracil