title: Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.
abstract: OBJECTIVE
  In 1992, preoperative radiotherapy was considered in France as the standard treatment for T3-4 rectal cancers. The present randomized trial compares preoperative radiotherapy with chemoradiotherapy.
  
  
  METHODS
  Patients were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in 25 fractions during 5 weeks was delivered. Concurrent chemotherapy with fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was administered during the first and fifth week in the experimental arm. Surgery was planned 3 to 10 weeks after the end of radiotherapy. All patients should receive adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary end point of the trial was overall survival.
  
  
  RESULTS
  A total of 733 patients were eligible. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter preservation. Complete sterilization of the operative specimen was more frequent with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5-year survival in the two groups did not differ.
  
  
  CONCLUSIONS
  Preoperative chemoradiotherapy despite a moderate increase in acute toxicity and no impact on overall survival significantly improves local control and is recommended for T3-4, N0-2, M0 adenocarcinoma of the middle and distal rectum.
authors.affiliation: Centre Antoine Lacassagne, Radiotherapy Department, Nice, France. jean-pierre.gerard@cal.nice.fnclcc.fr
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gérard
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Olivier
authors.initials: O
authors.lastname: Chapet
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Closon-Dejardin
authors.forename: Michel
authors.initials: M
authors.lastname: Untereiner
authors.forename: Bernard
authors.initials: B
authors.lastname: Leduc
authors.forename: Eric
authors.initials: E
authors.lastname: Francois
authors.forename: Jean
authors.initials: J
authors.lastname: Maurel
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Rémy
authors.initials: R
authors.lastname: Mackiewicz
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000379:methods*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D012008:Recurrence; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil