title: Neoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab, and pelvic radiotherapy: a phase II study in locally advanced rectal cancer.
abstract: OBJECTIVE
  Preoperative chemoradiotherapy followed by surgery represents the standard of care for locally advanced rectal cancer (LARC). Cetuximab has proved activity in advanced colorectal cancer, and its incorporation in preoperative treatment may increase tumor downstaging.
  
  
  METHODS
  After biopsy and staging, uT3/uT4 N0/+ LARC received single-agent cetuximab in three doses, followed by weekly cetuximab plus 5-fluorouracil (5-FU), concomitantly with RT. Sample size was calculated according to Bryant and Day test, a two-stage design with at least 10 pathologic complete remissions observed in 60 patients (pts) able to complete the treatment plan.
  
  
  RESULTS
  Forty pts with LARC were entered: male/female = 34/6; median age: 61 (range, 28-77); 12 uT3N0 Ed(30%); 25 uT3N1 (62%); 3 uT4N1 (8%); all Eastern Cooperative Oncology Group = 0. Thirty-five pts completed neoadjuvant treatment; 5 (12%) withdrew therapy after one cetuximab administration: three for hypersensitivity reactions, one for rapid progression, and one for purulent arthritis. They continued 5-FU in continuous infusion in association with RT. Thirty-one pts (77%) presented with acnelike rash; dose reduction/interruption of treatment was necessary in six pts (15%): two for Grade 3 acnelike rash, two for Grade 3 gastrointestinal toxicity, and two for refusal. Thirty-eight pts were evaluable for pathological response (one patient refused surgery, and one was progressed during neoadjuvant treatment). Pathological staging was: pT0N0 three pts (8%), pT1N0 1 pt (3%); pT2N0 13 pts (34%), and pT3 19 pts (50%) (N0:9, N1:5; N2:5); pT4 2 pts (5%).
  
  
  CONCLUSIONS
  Preoperative treatment with 5-FU, cetuximab, and pelvic RT is feasible with acceptable toxicities; however, the rate of pathologic responses is disappointingly low.
authors.affiliation: Division of Medical Oncology, Department of Oncology and Hematology, University Hospital, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertolini
authors.forename: Silvana
authors.initials: S
authors.lastname: Chiara
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bengala
authors.forename: Paolo
authors.initials: P
authors.lastname: Antognoni
authors.forename: Cristina
authors.initials: C
authors.lastname: Dealis
authors.forename: Sandra
authors.initials: S
authors.lastname: Zironi
authors.forename: Norma
authors.initials: N
authors.lastname: Malavasi
authors.forename: Tindaro
authors.initials: T
authors.lastname: Scolaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Depenni
authors.forename: Gordana
authors.initials: G
authors.lastname: Jovic
authors.forename: Claudia
authors.initials: C
authors.lastname: Sonaglio
authors.forename: Aldo
authors.initials: A
authors.lastname: Rossi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Luppi
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068818:Cetuximab; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D005472:Fluorouracil