Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203.
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.
Gérard
Jean-Pierre
JP
Centre Antoine Lacassagne, Radiotherapy Department, Nice, France. jean-pierre.gerard@cal.nice.fnclcc.fr
Conroy
Thierry
T
Bonnetain
Franck
F
Bouché
Olivier
O
Chapet
Olivier
O
Closon-Dejardin
Marie-Thérèse
MT
Untereiner
Michel
M
Leduc
Bernard
B
Francois
Eric
E
Maurel
Jean
J
Seitz
Jean-François
JF
Buecher
Bruno
B
Mackiewicz
Rémy
R
Ducreux
Michel
M
Bedenne
Laurent
L
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
D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil