Phase Ii Trial Of 5-Fluorouracil In Combination With Cisplatin And Concurrent Radiation Therapy (50.4 Gy) With Elective Nodal Irradiation For Clinical Stage Ii/Iii Esophageal Cancer

The Japan Clinical Oncology Group (JCOG) 9906 regimen is the standard therapy of definitive chemoradiation therapy for Japanese patients with esophageal cancer. This regimen consists of cisplatin at a dose of 40 mg/m2 on days 1, 8, 39, and 43 and continuous infusion of 5-fluorouracil at a dose of 400 mg/m2/d on days 1-5, 8-12, 36-40, and 43-46 plus concurrent radiation therapy with 2 weeks of planned interruption (60 Gy). However, there are problems to solve as to the JCOG9906 regimen, such as its high incidence of late toxicity, particularly pericardial effusion. This study is to evaluate the efficacy and toxicity of concurrent chemoradiation therapy with elective nodal irradiation (ENI) for stage II/III esophageal cancer to reduce the late toxicity, without compromising efficacy. Esophageal cancer patients with clinical stage II/III excluding T4 tumors were eligible. Concurrent chemotherapy was comprised of cisplatin at a dose of 75 mg/m2 on days 1, 29 and continuous infusion of 5-fluorouracil at a dose of 1000 mg/m2/d on days 1-4, 29-32. Radiation therapy was administered to a total dose of 50.4 Gy with ENI of 41.4 Gy. The regional lymph nodes for ENI included bilateral supraclavicular fossae and superior mediastinal lymph nodes for upper thoracic esophagus tumor, and mediastinal and perigastric lymph nodes for middle or lower thoracic esophagus tumor. Celiac axis lymph nodes were also included for lower thoracic esophagus tumor. Three or four fields technique was strongly recommended for middle or lower thoracic esophagus tumor. Between June 2006 and May 2008, 51 patients were enrolled. There were 6 females and 45 males whose median age was 64 years (range, 42-70 years). Thirty-one patients had T3 disease, while 42 had N1 disease. The clinical stages were II for 29 patients and III for 22 patients. Fifty patients were diagnosed with squamous cell carcinoma and one was diagnosed with adenosquamous cell carcinoma. Complete response was achieved in 36 patients (70.6%). With a median follow-up duration of 45 months, the 1- and 3-year overall survival rates were 88.2% and 62.7%, respectively. Acute toxicities included grade 3/4 anorexia (45%), esophagitis (35%), and febrile neutropenia (20%). Ten patients (19.6%) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery. With regard to late toxicities, grade ≧ 3 esophagitis, radiation pneumonitis, pleural effusion, pericardial effusion, and gastric hemorrhage developed in 3.9%, 5.9%, 0%, 0%, and 2.0% of the patients, respectively. Definitive chemoradiation therapy at a dose of 50.4 Gy with ENI achieved favorable survival rates with acceptable toxicities and can be a standard chemoradiation therapy for clinical stage II/III esophageal cancer.