Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2.
OBJECTIVE
Neoadjuvant chemoradiotherapy is considered a standard approach for T3-4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.


METHODS
We randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m(2) twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m(2) twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR).


RESULTS
Five hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P < .001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P = .09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P = .008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P = .02).


CONCLUSIONS
The benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3-4 rectal cancers.
Gérard
Jean-Pierre
JP
Centre Antoine Lacassagne, 06189 Nice cedex 2, France. jean-pierre.gerard@cal.nice.fnclcc.fr
Azria
David
D
Gourgou-Bourgade
Sophie
S
Martel-Laffay
Isabelle
I
Hennequin
Christophe
C
Etienne
Pierre-Luc
PL
Vendrely
Véronique
V
François
Eric
E
de La Roche
Guy
G
Bouché
Olivier
O
Mirabel
Xavier
X
Denis
Bernard
B
Mineur
Laurent
L
Berdah
Jean-François
JF
Mahé
Marc André
MA
Bécouarn
Yves
Y
Dupuis
Olivier
O
Lledo
Gérard
G
Montoto-Grillot
Christine
C
Conroy
Thierry
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; 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; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil