Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.
OBJECTIVE
To evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer.


METHODS
One hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT (50.4 Gy in 28 fractions). Capecitabine was administered concurrently at 1,650 mg/m2 on days 1 to 14 and 22 to 35, and oxaliplatin was administered at 50 mg/m2 on days 1, 8, 22, and 29. Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of adjuvant XELOX (capecitabine 1,000 mg/m2 bid on days 1 to 14; oxaliplatin 130 mg/m2 on day 1) were administered. The main end points were activity as assessed by the pathologic complete response (pCR) rate and the feasibility of postoperative XELOX chemotherapy.


RESULTS
After XELOX-RT, 103 of 104 eligible patients underwent surgery; pCR was achieved in 17 patients (16%), one patient had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of the tumor mass. R0 resections were achieved in 95% of patients, and sphincter preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients. Postoperative complication occurred in 43% of patients. Sixty percent of patients received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and diarrhea (12%) being the main grade 3 or 4 toxicities.


CONCLUSIONS
Preoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based treatment with XELOX- based multimodality treatment.
Rödel
Claus
C
Department of Radiotherapy, University of Erlangen-Nürnberg, Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de
Liersch
Torsten
T
Hermann
Robert Michael
RM
Arnold
Dirk
D
Reese
Thomas
T
Hipp
Matthias
M
Fürst
Alois
A
Schwella
Nimrod
N
Bieker
Michael
M
Hellmich
Gunter
G
Ewald
Hermann
H
Haier
Jörg
J
Lordick
Florian
F
Flentje
Michael
M
Sülberg
Heiko
H
Hohenberger
Werner
W
Sauer
Rolf
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use*; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D012074:Remission Induction; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil