A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with celecoxib and glutamine as first-line therapy for advanced colorectal cancer.
OBJECTIVE
Preclinical and clinical data indicate that cyclooxygenase-2 (COX-2) is a bona fide molecular target for colorectal cancer (CRC). Glutamine may decrease chemotherapy-associated diarrhea. This study was designed to address whether the addition of celecoxib, a COX-2 inhibitor, and glutamine would improve the efficacy and decrease the toxicities of the irinotecan, fluorouracil and leucovorin (IFL) regimen.


METHODS
All patients received the original IFL regimen plus celecoxib (400 mg, po, every 12 h continuously while on trial) and glutamine (10 g, po, every 8 h continuously while on chemotherapy).


RESULTS
Of the 41 patients enrolled, 40 patients received between 1 and 6 cycles of treatment. This regimen was associated with significant toxicities: 45.0% had grade 3 diarrhea, 35.0% grade 3/4 neutropenia, 22.5% hospitalization, 10.0% deep vein thrombosis and 2 treatment-related deaths. The overall response rate was 47.2%. The median progression-free survival was 6.7 months. The median overall survival was 16.3 months. The 12-month overall survival rate was 54.8%. COX-2 expression was present in 63.2% of the specimens evaluated. There was no significant correlation between COX-2 expression and response to chemotherapy (p = 0.739).


CONCLUSIONS
The addition of celecoxib and glutamine appears not to improve the efficacy or decrease the toxicities of IFL for the treatment of metastatic CRC.
Pan
Chong-Xian
CX
Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Ind. 46202, USA.
Loehrer
Patrick
P
Seitz
David
D
Helft
Paul
P
Juliar
Beth
B
Ansari
Rafat
R
Pletcher
William
W
Vinson
Jake
J
Cheng
Liang
L
Sweeney
Christopher
C
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005973:Glutamine / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D005973:Glutamine; D000077146:Irinotecan; D000068579:Celecoxib; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin