title: 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: OBJECTIVE
  This multicenter phase IB/II trial investigated cetuximab added to preoperative chemoradiotherapy for esophageal cancer.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Fachbereich Onkologie/Hämatologie, Kantonsspital St Gallen, CH-9007 St Gallen, Switzerland. thomas.ruhstaller@kssg.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruhstaller
authors.forename: Miklos
authors.initials: M
authors.lastname: Pless
authors.forename: Daniel
authors.initials: D
authors.lastname: Dietrich
authors.forename: Helmut
authors.initials: H
authors.lastname: Kranzbuehler
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.forename: Peter
authors.initials: P
authors.lastname: Moosmann
authors.forename: Michael
authors.initials: M
authors.lastname: Montemurro
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauch
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.forename: Walter
authors.initials: W
authors.lastname: Mingrone
authors.forename: Lucas
authors.initials: L
authors.lastname: Widmer
authors.forename: Roman
authors.initials: R
authors.lastname: Inauen
authors.forename: Peter
authors.initials: P
authors.lastname: Brauchli
authors.forename: Viviane
authors.initials: V
authors.lastname: Hess
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013505:Digestive System Surgical Procedures; D000077143:Docetaxel; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020360:Neoadjuvant Therapy / Q000379:methods*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin