A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with celecoxib and glutamine as first-line therapy for advanced colorectal cancer.

Objectives: 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).

Conclusion: The addition of celecoxib and glutamine appears not to improve the efficacy or decrease the toxicities of IFL for the treatment of metastatic CRC.