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)

Abstract

Purpose: This multicenter phase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer. Patients and Methods: Patients with resectable, locally advanced esophageal cancer received two 3-week cycles of induction chemoimmunotherapy (cisplatin 75 mg/m2 day 1, docetaxel 75 mg/m2 day 1, cetuximab 250 mg/m2 days 1, 8,15 [400 mg/m2 loading dose]) followed by chemoimmunoradiation therapy (CIRT) and surgery. CIRT consisted of 45 Gy radiotherapy (RT) plus concurrent cisplatin 25 mg/m2 and cetuximab 250 mg/m2 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 X 5). If fewer than three patients experienced LTs, 13 additional patients were treated at this dose. Results: 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. Conclusion: 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. © 2011 by American Society of Clinical Oncology.