title: Effect of neoadjuvant cetuximab, capecitabine, and radiotherapy for locally advanced rectal cancer: results of a phase II study.
abstract: OBJECTIVE
  The aim of this study was to investigate the efficacy and safety of neoadjuvant cetuximab, capecitabine, and radiotherapy for patients with locally advanced rectal cancer.
  
  
  METHODS
  Sixty-three eligible patients were selectively enrolled in this study. Neoadjuvant treatment consisted of cetuximab and capecitabine for 6 weeks and radiotherapy for 5 weeks. Surgical resection was performed 6-8 weeks after the completion of neoadjuvant treatment. KRAS mutation statuses were analyzed retrospectively after the cetuximab treatment. All the patients underwent a standardized postoperative follow-up for at least 3 years.
  
  
  RESULTS
  A pathological complete response (pCR) was achieved in eight patients (12.7 %). Overall down-staging was found in 49 patients (77.8 %). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate was 76.2 % and 81.0 %, respectively. The most common adverse events during neoadjuvant treatment were acneiform skin rash (82.5 %), radiodermatitis (46.0 %), and diarrhea (36.5 %). KRAS mutations were detected in 19 of 63 (31.2 %) tumors. The down-staging rate in patients with KRAS wild-type (WT) was significantly higher than patients with KRAS mutation (P = 0.020). There was no significant difference in the pCR rate, 3-year DFS rate or 3-year OS rate between KRAS WT patients and KRAS-mutated patients.
  
  
  CONCLUSIONS
  Neoadjuvant treatment with cetuximab and capecitabine-based chemoradiotherapy is safe and well tolerated. The pCR rate, 3-year DFS rate and OS rate are not superior to the rate of neoadjuvant chemoradiotherapy using two or more cytotoxic agents. The KRAS WT is highly associated with tumor down-staging to cetuximab plus capecitabine-based CRT in patients with LARC.
authors.affiliation: Center of Transplant Medicine Engineering and Technology of Ministry of Health of The People´s Republic of China, The Third Xiangya Hospital of Central South University, Changsha, China. peilong@sh163.net
authors.forename: Pei-Long
authors.initials: PL
authors.lastname: Sun
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Ye
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D000068818:Cetuximab; D059248:Chemoradiotherapy / Q000009:adverse effects; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D005472:Fluorouracil