title: Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.
abstract: BACKGROUND
  The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes.
  
  
  METHODS
  Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS).
  
  
  RESULTS
  A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively.
  
  
  CONCLUSIONS
  Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.
authors.affiliation: Department of Medical Oncology, Valencian Institute of Oncology, Valencia, Spain cfmartos@fivo.org.
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Martos
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
authors.forename: X
authors.initials: X
authors.lastname: Garcia-Albeniz
authors.affiliation: Department of Medical Oncology, Parc Taulí Hospital, Sabadell.
authors.forename: C
authors.initials: C
authors.lastname: Pericay
authors.affiliation: Department of Medical Oncology, Clinic Hospital, Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Maurel
authors.affiliation: Department of Medical Oncology, La Fe University Hospital, Valencia.
authors.forename: J
authors.initials: J
authors.lastname: Aparicio
authors.affiliation: Department of Medical Oncology, Del Mar Hospital, Barcelona.
authors.forename: C
authors.initials: C
authors.lastname: Montagut
authors.affiliation: Department of Medical Oncology, General University Hospital, Valencia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Safont
authors.affiliation: Department of Medical Oncology, Arnau de Vilanova Hospital, Lleida.
authors.forename: A
authors.initials: A
authors.lastname: Salud
authors.affiliation: Department of Medical Oncology, Navarra Hospital, Pamplona.
authors.forename: R
authors.initials: R
authors.lastname: Vera
authors.affiliation: Department of Medical Oncology, General Hospital, Alicante.
authors.forename: B
authors.initials: B
authors.lastname: Massuti
authors.affiliation: Department of Medical Oncology, Lozano Blesa Hospital, Zaragoza.
authors.forename: P
authors.initials: P
authors.lastname: Escudero
authors.affiliation: Department of Medical Oncology, Miguel Servet Hospital, Zaragoza.
authors.forename: V
authors.initials: V
authors.lastname: Alonso
authors.affiliation: Department of Medical Oncology, Pesset Hospital, Valencia.
authors.forename: C
authors.initials: C
authors.lastname: Bosch
authors.affiliation: Department of Medical Oncology, Santa Creu y Sant Pau Hospital, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.affiliation: Division of Radiation Oncology, MD Anderson Hospital, Houston, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Minsky
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000379:methods*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000628:therapy*; D012007:Rectum / Q000601:surgery*
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine
keywords: induction chemotherapy; locally advanced rectal cancer; phase II randomized trial, adjuvant chemotherapy