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/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.

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.

• Authors: Thomas Ruhstaller, Miklos Pless, Daniel Dietrich, Helmut Kranzbuehler, Roger von Moos, Peter Moosmann, Michael Montemurro, Paul M Schneider, Daniel Rauch, Oliver Gautschi, Walter Mingrone, Lucas Widmer, Roman Inauen, Peter Brauchli, Viviane Hess
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 6 Pg. 626-31 (Feb 20 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21205757 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Taxoids
• Docetaxel
• Cetuximab
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, radiotherapy, surgery)
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy, surgery)
• Cetuximab
• Cisplatin (administration & dosage, adverse effects, therapeutic use)
• Digestive System Surgical Procedures
• Docetaxel
• Esophageal Neoplasms (drug therapy, radiotherapy, surgery)
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Multicenter Studies as Topic
• Neoadjuvant Therapy (methods)
• Taxoids (administration & dosage, adverse effects, therapeutic use)