title: Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer.
abstract: BACKGROUND
  Cetuximab improves activity of chemotherapy in metastatic colorectal cancer (mCRC). Gene copy number (GCN) of epidermal growth factor receptor (EGFR) has been suggested to be a predictive factor of response to cetuximab in patients (pts) with mCRC; on the contrary, K-ras mutation has been associated with cetuximab resistance.
  
  
  METHODS
  We have conducted a phase II study with cetuximab administered weekly for 3 weeks as single agent and then with 5-fluorouracil and radiation therapy as neo-adjuvant treatment for locally advanced rectal cancer (LARC). EGFR immunohistochemistry expression, EGFR GCN and K-ras mutation were evaluated on diagnostic tumor biopsy. Dworak's tumor regression grade (TRG) was evaluated on surgical specimens.
  
  
  RESULTS
  Forty pts have been treated; 39 pts are assessable. TRG 3 and 4 were achieved in nine (23.1%) and three pts (7.7%) respectively; TRG 3-4 rate was 55% and 5.3% in case of high and low GCN, respectively (P 0.0016). Pts with K-ras mutated tumors had lower rate of high TRG: 11% versus 36.7% (P 0.12). In pts with wild-type K-ras, TRG 3-4 rate was 58.8% versus 7.7% in case of high or low GCN, respectively (P 0.0012).
  
  
  CONCLUSIONS
  In pts with LARC, EGFR GCN is predictive of high TRG to cetuximab plus 5-FU radiotherapy. Moreover, our data suggest that a wild-type K-ras associated with a high EGFR GCN can predict sensitivity to cetuximab-based treatment.
authors.affiliation: Division of Medical Oncology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy. bengala.carmelo@unimore.it
authors.forename: C
authors.initials: C
authors.lastname: Bengala
authors.forename: S
authors.initials: S
authors.lastname: Bettelli
authors.forename: F
authors.initials: F
authors.lastname: Bertolini
authors.forename: S
authors.initials: S
authors.lastname: Salvi
authors.forename: S
authors.initials: S
authors.lastname: Chiara
authors.forename: C
authors.initials: C
authors.lastname: Sonaglio
authors.forename: L
authors.initials: L
authors.lastname: Losi
authors.forename: N
authors.initials: N
authors.lastname: Bigiani
authors.forename: G
authors.initials: G
authors.lastname: Sartori
authors.forename: C
authors.initials: C
authors.lastname: Dealis
authors.forename: N
authors.initials: N
authors.lastname: Malavasi
authors.forename: R
authors.initials: R
authors.lastname: D'Amico
authors.forename: G
authors.initials: G
authors.lastname: Luppi
authors.forename: B
authors.initials: B
authors.lastname: Gatteschi
authors.forename: A
authors.initials: A
authors.lastname: Maiorana
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011300:Preoperative Care; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000068818:Cetuximab; D005472:Fluorouracil