title: Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.
abstract: BACKGROUND
  To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer.
  
  
  METHODS
  Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level).
  
  
  RESULTS
  Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response.
  
  
  CONCLUSIONS
  Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.
authors.affiliation: Clinique des Pathologies Tumorales du Côlon et du Rectum, Centre du Cancer, Université catholique de Louvain, Cliniques universitaires Saint-Luc, 10 avenue Hippocrate, 1200 Brussels, Belgium. jean-pascal.machiels@onco.ucl.ac.be
authors.forename: J-P
authors.initials: JP
authors.lastname: Machiels
authors.forename: C
authors.initials: C
authors.lastname: Sempoux
authors.forename: P
authors.initials: P
authors.lastname: Scalliet
authors.forename: J-C
authors.initials: JC
authors.lastname: Coche
authors.forename: Y
authors.initials: Y
authors.lastname: Humblet
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: J
authors.initials: J
authors.lastname: Kerger
authors.forename: J-L
authors.initials: JL
authors.lastname: Canon
authors.forename: M
authors.initials: M
authors.lastname: Peeters
authors.forename: S
authors.initials: S
authors.lastname: Aydin
authors.forename: S
authors.initials: S
authors.lastname: Laurent
authors.forename: A
authors.initials: A
authors.lastname: Kartheuser
authors.forename: B
authors.initials: B
authors.lastname: Coster
authors.forename: S
authors.initials: S
authors.lastname: Roels
authors.forename: J-F
authors.initials: JF
authors.lastname: Daisne
authors.forename: B
authors.initials: B
authors.lastname: Honhon
authors.forename: L
authors.initials: L
authors.lastname: Duck
authors.forename: C
authors.initials: C
authors.lastname: Kirkove
authors.forename: M-A
authors.initials: MA
authors.lastname: Bonny
authors.forename: K
authors.initials: K
authors.lastname: Haustermans
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D000068818:Cetuximab; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D020266:Radiotherapy, Conformal / Q000379:methods*; D012004:Rectal Neoplasms / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil