Double blind randomized phase II study with radiation+5-fluorouracil+/-celecoxib for resectable rectal cancer.
OBJECTIVE
To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind randomized phase II study.


METHODS
Thirty-five patients of the initially planned 80 patients with locally advanced rectal cancer were treated with preoperative radiation (45 Gy; 1.8 Gy/fraction, 5 days/week) combined with 5-fluorouracil (continuous infusion, 225 mg/m(2)/day) and celecoxib (2 x 400 mg/day) or placebo. Pathological response and toxicity of study treatment were evaluated, as well as expression of COX-2 and Ki67 in tumor tissue and IL-6 in plasma as possible molecular correlates and predictors of response to treatment.


RESULTS
Patients treated with celecoxib tended to show a better response (61%) when compared to those treated with placebo (35%), although not significant (p=0.13). T-downstaging and N-downstaging were also slightly higher with celecoxib. Plasma IL-6 levels and intratumoral COX2 or Ki67 were altered by chemoradiation, but were not further altered by celecoxib treatment and therefore not useful for prediction of treatment benefit. Celecoxib therapy in conjunction with chemoradiation was not associated with additional toxicity and seemed to help mitigate therapy-related pain.


CONCLUSIONS
Addition of celecoxib to preoperative chemoradiation is feasible for patients with locally advanced rectal cancer. To study the individual effect of COX-2 inhibitors on pathological response phase III studies are required.
Debucquoy
Annelies
A
Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. annelies.debucquoy@med.kuleuven.be
Roels
Sarah
S
Goethals
Laurence
L
Libbrecht
Louis
L
Van Cutsem
Eric
E
Geboes
Karel
K
Penninckx
Freddy
F
D'Hoore
André
A
McBride
William H
WH
Haustermans
Karin
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068579:Celecoxib; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000628:therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects
D015850:Interleukin-6; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D005472:Fluorouracil