title: Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial.
abstract: OBJECTIVE
  To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer.
  
  
  METHODS
  Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed.
  
  
  RESULTS
  A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively.
  
  
  CONCLUSIONS
  Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.
authors.affiliation: Department of Oncology, Clínica Universidad de Navarra, Pamplona, Navarra, Spain. larbea@unav.es
authors.forename: Leire
authors.initials: L
authors.lastname: Arbea
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.forename: Juan A
authors.initials: JA
authors.lastname: Díaz-González
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Hernández
authors.forename: Jesús Javier
authors.initials: JJ
authors.lastname: Sola
authors.forename: Luis Isaac
authors.initials: LI
authors.lastname: Ramos
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Subtil
authors.forename: Jorge
authors.initials: J
authors.lastname: Nuñez
authors.forename: Ana
authors.initials: A
authors.lastname: Chopitea
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.forename: Miren
authors.initials: M
authors.lastname: Gaztañaga
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
authors.forename: Javier
authors.initials: J
authors.lastname: Aristu
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010349:Patient Compliance; D011300:Preoperative Care / Q000379:methods; D011349:Proctitis / Q000209:etiology / Q000473:pathology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil