Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer:: a GERCOR study

Background: Oxaliplatin stop and go in combination with leucovorin and 5-fluorouracil has been successfully used in a previous study (OPTIMOX1) in metastatic colorectal cancer (MCR). Celecoxib is an anti-cyclooxygenase-2 drug with anti-neoplastic properties. In the present study, celecoxib was evaluated in combination with FOLFOX7 regimen and as a single agent in maintenance therapy. Patients and methods: This phase II study examined for previously untreated MCR patients the stop-and-go procedure [six cycles of folinic acid, 5FU and oxaliplatin (FOLFOX7) followed by chemotherapy-free intervals (CFIs) and reintroduction at progression] with continuous administration of celecoxib (800 mg/day). Results: Forty-four patients were included, 42 eligible: performance status (%) 0/1/2 = 45/40/15, median age 60 (31-76) years. Response rate (RR) was 43% (95% CI 28%-58%). Median progression-free survival (PFS) was 6 months; median overall survival was 15.8 months. Grade 3/4 toxicity criteria were neurotoxicity 9.5%, thrombocytopenia 21.4%, neutropenia 7.1%, diarrhea 7.1%, nausea 4.8% and vomiting 2.4%. Median CFI 1 (n = 27) duration was 3.9 months (range 2-39 months). Conclusion: With an acceptable safety profile, celecoxib combined with FOLFOX7 achieved RR and PFS in the lower range of that obtained with FOLFOX7 alone. These results indicate the lack of synergy between FOLFOX7 and celecoxib. PFS of 6 months appears lower than PFS obtained in OPTIMOX1 study with simplified LV5FU2 in maintenance therapy.