Cetuximab in Combination With Chemoradiotherapy Before Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma: A Prospective, Multicenter Phase IB/II Trial (SAKK 75/06)

• Published in: Journal of clinical oncology Vol. 29; no. 6; pp. 626 - 631
• Main Authors: RUHSTALLER, Thomas, PLESS, Miklos, MINGRONE, Walter, WIDMER, Lucas, INAUEN, Roman, BRAUCHLI, Peter, HESS, Viviane, DIETRICH, Daniel, KRANZBUEHLER, Helmut, VON MOOS, Roger, MOOSMANN, Peter, MONTEMURRO, Michael, SCHNEIDER, Paul M, RAUCH, Daniel, GAUTSCHI, Oliver
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.02.2011
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - radiotherapy; Adenocarcinoma - surgery; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - radiotherapy; Carcinoma, Squamous Cell - surgery; Cetuximab; Cisplatin - administration & dosage; Cisplatin - adverse effects; Cisplatin - therapeutic use; Digestive System Surgical Procedures; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - surgery; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multicenter Studies as Topic; Neoadjuvant Therapy - methods; Taxoids - administration & dosage; Taxoids - adverse effects; Taxoids - therapeutic use; Tumors; Antineoplastic agent; Human; Drug combination; Multicenter study; Esophageal disease; Esophagus carcinoma; Monoclonal antibody; Malignant tumor; Chemoradiotherapy; Epidermal growth factor receptor; Esophagus cancer; Prospective; Cancerology; Treatment; Surgery; Phase II trial; Digestive diseases; Locally advanced stage; Cetuximab; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.31.9715

This multicenter phase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer. Patients with resectable, locally advanced esophageal cancer received two 3-week cycles of induction chemoimmunotherapy (cisplatin 75 mg/m(2) day 1, docetaxel 75 mg/m(2) day 1, cetuximab 250 mg/m(2) days 1, 8,15 [400 mg/m(2) loading dose]) followed by chemoimmunoradiation therapy (CIRT) and surgery. CIRT consisted of 45 Gy radiotherapy (RT) plus concurrent cisplatin 25 mg/m(2) and cetuximab 250 mg/m(2) weekly for 5 weeks in cohort 1. If fewer than three of seven patients experienced limiting toxicity (LT), the next seven patients also received docetaxel (20 mg/m(2) weekly × 5). If fewer than three patients experienced LTs, 13 additional patients were treated at this dose. In total, 28 patients (median age, 64 years) with predominantly node-positive (82%) esophageal adenocarcinoma (15 patients) or squamous cell carcinoma (13 patients) were enrolled and 24 (86%) completed the entire trimodal therapy. During CIRT, no LT occurred, rash was not exacerbated within the RT field, and the main grade 3 toxicities were esophagitis (seven patients), anorexia (three), fatigue (three), and thrombosis (two). Surgery (R0 resection) was performed in 25 patients. Anastomotic leakage occurred in three patients: two recovered spontaneously and one successfully underwent re-operation. There were no deaths at 30 days and no treatment-related mortality after 12 months. Nineteen patients (68%) showed complete or near complete pathologic regression. Adding cetuximab to preoperative chemoradiotherapy is feasible without increasing postoperative mortality. Phase III investigation has begun based on the high histopathologic response and R0 resection rate.