title: A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer.
abstract: BACKGROUND
  Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC.
  
  
  METHODS
  Patients with stage II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250 mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR).
  
  
  RESULTS
  Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis.
  
  
  CONCLUSIONS
  Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.
authors.affiliation: Department of Radiotherapy, Institute of Oncology, Ljubljana, Slovenia. vvelenik@onko-i.si
authors.forename: V
authors.initials: V
authors.lastname: Velenik
authors.forename: J
authors.initials: J
authors.lastname: Ocvirk
authors.forename: I
authors.initials: I
authors.lastname: Oblak
authors.forename: F
authors.initials: F
authors.lastname: Anderluh
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000069287:Capecitabine; D000068818:Cetuximab; D003082:Colectomy / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D066246:ErbB Receptors; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011355:Prodrugs; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011355:Prodrugs; D003841:Deoxycytidine; D000069287:Capecitabine; D066246:ErbB Receptors; D000068818:Cetuximab; D005472:Fluorouracil