Phase III trial of irinotecan plus oxaliplatin (IROX) versus irinotecan plus 5-FU/folinic acid (FOLFIRI) as first-line treatment of metastatic colorectal cancer (CRC): The FIRE-Trial

Abstract

3516 Objective: This randomised cross-over study compares the 1st-line efficacy and toxicity of infusional 5-FU/FA (AIO regimen) plus irinotecan (FOLFIRI) to the combination of irinotecan plus oxaliplatin (IROX). Methods: 488 patients (pts) from 56 centres were enrolled between July 2000 and the end of study in September 2004. In the FOLFIRI arm, pts received FA 500mg/m2 plus 5-FU 2000 mg/m2 (24h) and irinotecan 80mg/m2 given weekly for 6 times. In the IROX arm pts were treated with oxaliplatin 85mg/m2 (d1, 15, 29) and irinotecan 80mg/m2 weekly times 6. Treatment cycles were repeated on day 50 in both treatment arms. Patients were stratified according to LDH, adjuvant pretreatment, and Karnofsky performance status (KPS) showing LDH >240 U/ml in 42% vs 39%, adjuvant pretreatment in 31% vs 29%, and a KPS=100% in 48% vs 47%, in the FOLFIRI- and IROX-arm respectively. The primary end-point of the trial was progression-free survival. At disease progression, pts were offered to switch to the comparator regimen. Results: At the time of analysis, treatment efficacy was evaluable in 299 pts (157 FOLFIRI, 142 IROX). The complete remission rate (CR) was 8% in both arms, the partial remission rate (PR) 38% vs 42% for an overall remission rate (CR+PR) of 46% vs 50%. Stable disease (SD) was documented in 47% vs 33% resulting in a disease control rate (CR+PR+SD) of 92% vs 83%. In the FOLFIRI- and the IROX-arm respectively, median progression-free survival was 8.7 months (95% CI, 7.3–9,6) vs 7.3 months (95% CI, 6.4–8.2) (p=0.15), while median overall survival was 21.1 months (95% CI, 18.8–27.2) vs 18.6 months (95% CI, 16.3–22.8) (p=0.23). Treatment was stopped due to toxicity in 8.5% vs 16.5%, and 60-day mortality was 5.5% and 3.4% (FOLFIRI vs IROX). Conclusions: FOLFIRI and IROX are comparably effective with regard to response, progression-free survival, and overall survival. Toxicity is similarly acceptable in both treatment arms. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Pharma Germany