title: Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial.
abstract: BACKGROUND
  The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma.
  
  
  METHODS
  We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR).
  
  
  RESULTS
  On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%-85%), and the 2-year local relapse rate was 2% (95% CI: 0%-11%).
  
  
  CONCLUSIONS
  In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials.
authors.affiliation: Fundacion Instituto Valenciano de Oncología, Valencia, Spain; cfmartos@fivo.org.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Martos
authors.affiliation: Royal Marsden Hospital, London and Surrey, United Kingdom;
authors.forename: Gina
authors.initials: G
authors.lastname: Brown
authors.affiliation: Fundacion Instituto Valenciano de Oncología, Valencia, Spain;
authors.forename: Rafael
authors.initials: R
authors.lastname: Estevan
authors.affiliation: Hospital Arnau de Vilanova, Lleida, Spain;
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salud
authors.affiliation: Hospital del Mar, Barcelona, Spain;
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.affiliation: Hospital Clinic, Barcelona, Spain;
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.affiliation: Hospital General Univeristario, Valencia, Spain;
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Safont
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain;
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain;
authors.forename: Jaime
authors.initials: J
authors.lastname: Feliu
authors.affiliation: Hospital de Navarra, Pamplona, Spain;
authors.forename: Ruth
authors.initials: R
authors.lastname: Vera
authors.affiliation: Hospital Miguel Servet, Zaragoza, Spain;
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
authors.affiliation: Hospital General, Elche, Spain;
authors.forename: Javier
authors.initials: J
authors.lastname: Gallego
authors.affiliation: Hospital Santa Creu y Sant Pau, Barcelona, Spain;
authors.forename: Marta
authors.initials: M
authors.lastname: Martin
authors.affiliation: Hospital del Mar, Barcelona, Spain;
authors.forename: Miguel
authors.initials: M
authors.lastname: Pera
authors.affiliation: Hospital Arnau de Vilanova, Lleida, Spain;
authors.forename: Enrique
authors.initials: E
authors.lastname: Sierra
authors.affiliation: Corporación Sanitaria Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Serra
authors.affiliation: Hospital Clinic, Barcelona, Spain;
authors.forename: Salvadora
authors.initials: S
authors.lastname: Delgado
authors.affiliation: Hospital General Univeristario, Valencia, Spain;
authors.forename: Jose V
authors.initials: JV
authors.lastname: Roig
authors.affiliation: Fundacion Instituto Valenciano de Oncología, Valencia, Spain;
authors.forename: Jesus
authors.initials: J
authors.lastname: Santos
authors.affiliation: Corporación Sanitaria Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D012007:Rectum / Q000601:surgery
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine