Comparison of the tolerance and efficacy of LV5FU2-CPT11 and FOLFIRI regimens in front-line treatment of advanced colorectal cancer -A pooled analysis of 254 patients included in 2 randomised trials.

3576 Background: With only one 5FU bolus injection and an increased dose of 5FU by continuous infusion, the simplified LV5FU2 regimen is considered as effective as but less toxic and more convenient than the original LV5FU2 de Gramont regimen [Tournigand ASCO 1998 #1052]. LV5FU2-CPT11 and FOLFIRI are safe and active in the front-line treatment of metastatic colorectal cancer [Douillard Lancet 2000 -V303 trial, Tournigand JCO 2004 -V308 trial]. In both regimens, CPT11 is given at a dose of 180 mg/m2 combined with the LV5FU2 regimen for LV5FU2-CPT11 or with the simplified LV5FU2 regimen for FOLFIRI. METHODS We performed a comparison based on the individual data from the V303 and V308 trials to assess the safety profile and efficacy of LV5FU2-CPT11 and FOLFIRI. Main severe adverse events (NCI grade 3-4) possibly and probably related to treatment as well as the objective response rate (ORR) and progression-free survival (PFS) were compared by treatment group. RESULTS 145 pts received the LV5FU2-CPT11 combination in the V303 trial and 109 pts received the FOLFIRI regimen in the V308 trial. Pre-treatment characteristics appeared to be similar in the two groups except for the sex-ratio (F: LV5FU2-CPT11: 29.0%, FOLFIRI: 43.1%) and number of metastatic sites (≥3 sites: LV5FU2-CPT11: 14.5%, FOLFIRI: 4.6%). Severe neutropenia (24% vs. 45%, p=0.001) and asthenia (4% vs. 9%, ns) were less frequent whereas mucositis (10% vs. 4%, ns), nausea and vomiting (10% vs. 3%; ns) were more frequent with the FOLFIRI regimen. The frequency of severe diarrhea was 14% in both groups. ORR: LV5FU2-CPT11: 33.1% [95CI: 25.5-41.4], FOLFIRI: 56.0% [95CI: 46.1-65.5] (p<0.01, HR= 1.2 [1.1-1.3]. PFS: LV5FU2-CPT11: 5.7 months [95CI: 4.1-6.7], FOLFIRI: 8.5 months [95CI: 7.0-9.5] (ns). CONCLUSIONS This non-randomized retrospective comparison suggests that the FOLFIRI regimen has a different toxicity profile and may have higher efficacy than the LV5FU2-CPT11 regimen. [Table: see text].