Oxaliplatin (L-OHP) combined with irinotecan (CPT-11), leucovorin (LV) and fluorouracil (5-FU) compared with irinotecan, leucovorin and fluorouracil as first-line treatment for metastatic colorectal cancer (MCC): Preliminary results of a multicenter randomized phase III trial

3532 Background: In a phase II trial conducted from our group the 4-drug regimen (5FU+LV+CPT-11+L-OHP) was highly active and well tolerated (JCO 2002;20:2661–2667). A randomized trial was conducted to compare in terms of overall survival (OS) the 4-drug regimen (Arm-A) with the “standard” 3-drug (5FU+LV+CPT-11) FOLFIRI regimen (Arm-B) as first-line treatment in MCC Methods: Assuming OS 17months for Arm-B and 21 months for Arm-A, 276 pts were needed to show a significant difference (two-tailed log-rank test; a=0.05, b=0.8). For Arm-A CPT-11 150mg/m2 30–90 min infusion was given on d1, L-OHP 65mg/m2 2h infusion on d2, simultaneously but in different lines with LV 200mg/m2 on days 2+3 followed by 5-FU 400 mg/m2/d iv bolus and 600 mg/m2/d 22h infusion on days 2+3. For Arm-B CPT-11 180mg/m2 30–90 min infusion was given on d1, LV 200 mg/m2 on days 1+2 followed by 5-FU 400 mg/m2/d iv bolus and 600 mg/m2/d 22h infusion on days 1+2. Cycles were repeated every 2 weeks until disease progression, unacceptable toxicity or consent withdrawal. Results: As of today 203 pts and 1673 cy of therapy were evaluable for safety and efficacy. 101 pts on Arm-A: M/F: 62/39, PS 0/1/2: 59/30/12, median age 65 (25–75).102 pts on Arm-B: M/F: 57/45, PS 0/1/2: 47/39/16, median age 66 (42–80). In an intention-to-treat analysis the response rate was 45% (95%CI 35,45%–55,27%) in Arm-A and 31% (95%CI 22,68%–41,24%) in Arm-B (p=0,055). In addition 32% of pts presented stable disease in Arm-A and 23% in Arm-B (p=0,147). Disease progression was observed in 23% of pts in Arm-A and 45% in Arm-B(p=0,001). Median TTP was 8.9 and 6.1 months (p=0,0958) and OS 21.1 and 16.5 months in Arm-A and Arm-B, respectively (Log rank=0,0956). Conclusions: These preliminary results show promising efficacy with acceptable safety for the 4-drug combination. Updated data will be presented. No significant financial relationships to disclose.