title: Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin.
abstract: OBJECTIVE
  To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer.
  
  
  METHODS
  A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival.
  
  
  RESULTS
  Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55).
  
  
  CONCLUSIONS
  Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.
authors.affiliation: Department of Radiation Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. oncrtcph@saludalia.com
authors.forename: Alejandro
authors.initials: A
authors.lastname: de la Torre
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: García-Berrocal
authors.forename: Fernando
authors.initials: F
authors.lastname: Arias
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mariño
authors.forename: Francisco
authors.initials: F
authors.lastname: Valcárcel
authors.forename: Rosa
authors.initials: R
authors.lastname: Magallón
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Regueiro
authors.forename: Jesús
authors.initials: J
authors.lastname: Romero
authors.forename: Irma
authors.initials: I
authors.lastname: Zapata
authors.forename: Cristina
authors.initials: C
authors.lastname: de la Fuente
authors.forename: Eva
authors.initials: E
authors.lastname: Fernández-Lizarbe
authors.forename: Gloria
authors.initials: G
authors.lastname: Vergara
authors.forename: Belén
authors.initials: B
authors.lastname: Belinchón
authors.forename: Maria
authors.initials: M
authors.lastname: Veiras
authors.forename: Rafael
authors.initials: R
authors.lastname: Molerón
authors.forename: Isabel
authors.initials: I
authors.lastname: Millán
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage; D014803:Vitamin B Complex / Q000008:administration & dosage
chemical_list: D014803:Vitamin B Complex; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin; D005472:Fluorouracil