title: Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer.
abstract: OBJECTIVE
  To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy.
  
  
  METHODS
  Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively.
  
  
  RESULTS
  No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2.
  
  
  CONCLUSIONS
  The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.
authors.affiliation: Service of Radiation Oncology, Department of Oncology, Clínica Universitaria, University of Navarre, Pamplona, Spain. jjaristu@unav.es
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Aristu
authors.forename: Leire
authors.initials: L
authors.lastname: Arbea
authors.forename: Javier
authors.initials: J
authors.lastname: Rodriguez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Hernández-Lizoain
authors.forename: Jesús Javier
authors.initials: JJ
authors.lastname: Sola
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Azcona
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Díaz-González
authors.forename: Jesús Miguel
authors.initials: JM
authors.lastname: García-Foncillas
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011300:Preoperative Care / Q000379:methods*; D020266:Radiotherapy, Conformal / Q000379:methods*; D012004:Rectal Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil