Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

• Published in: International journal of radiation oncology, biology, physics Vol. 89; no. 4; pp. 872 - 879
• Main Authors: Higuchi, Katsuhiko, Komori, Shouko, Tanabe, Satoshi, Katada, Chikatoshi, Azuma, Mizutomo, Ishiyama, Hiromichi, Sasaki, Tohru, Ishido, Kenji, Katada, Natsuya, Hayakawa, Kazushige, Koizumi, Wasaburo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2014
• Subjects: Aged; Anemia - etiology; ANOREXIA; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; CHEMOTHERAPY; Cisplatin - administration & dosage; CLASSIFICATION; Disease-Free Survival; Drug Administration Schedule; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophagitis - prevention & control; ESOPHAGUS; Feasibility Studies; Febrile Neutropenia; Female; Fluorouracil - administration & dosage; Hematology, Oncology and Palliative Medicine; Humans; IRRADIATION; LEUKOPENIA; Leukopenia - etiology; LYMPH NODES; Lymphatic Irradiation - methods; Lymphatic Metastasis; Male; METASTASES; Middle Aged; Neoplasm Staging; NEOPLASMS; Neutropenia - etiology; PATIENTS; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; Taxoids - administration & dosage; TOXICITY; URACILS
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2014.03.030

A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m2) and cisplatin (40 mg/m2) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m2/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.