FOLFIRI Preferred Over IROX for First-Line Treatment of Metastatic Colorectal Cancer

MUNICH, GERMANY-Irinotecan (Camptosar) plus fluorouracil(Drug information on fluorouracil) (5-FU)/folinic acid (FOLFIRI) is significantly better at controlling metastatic colorectal cancer (CRC) than irinotecan(Drug information on irinotecan)/oxaliplatin (Eloxatin)(IROX) and should be the preferred first-line treatment, Andreas Schalhorn, MD, of Klin Grosshadern in Munich, said (abstract 3516). Delayed toxicity rates also favored FOLFIRI. FIRE Trial Dr. Schalhorn reported the FIRE trial, a phase III randomized crossover study that compared the first-line efficacy and toxicity of infusional 5-FU/ FA (the AIO regimen) plus irinotecan (FOLFIRI) with IROX. The study enrolled 488 patients from 56 centers between July 2000 and September 2004. Patients in the FOLFIRI arm received folinic acid (500 mg/m²) plus 5-FU (2,000 mg/m² as a 24-hour infusion) plus irinotecan (80 mg/m² given weekly for 6 weeks). Patients in the IROX arm were treated with oxaliplatin(Drug information on oxaliplatin) (85 mg/m² on days 1, 15, and 29) and irinotecan (80 mg/m²) weekly for 6 weeks. Treatment cycles were repeated on day 50 in both treatment arms. The primary endpoint was progression-free survival, and patients were allowed to cross over to the comparator regimen at disease progression. Dr. Schalhorn presented efficacy data for 299 patients (157 FOLFIRI, 142 IROX). The complete remission rate was 8% in both arms. The partial remission rate was 37% with FOLFIRI vs 40% with IROX, for an overall remission rate of 45% vs 48% (P = nonsignificant). Stable disease was documented in 44% of FOLFIRI patients vs 31% of IROX patients (P =.004), resulting in a disease control rate of 89% vs 79% (P = .004). Improvement in Survival Median progression-free survival was 8.2 months with FOLFIRI (95% confidence interval [CI], 7.3-9.6) vs 7.0 months with IROX (95% CI, 6.4- 8.2; P = .15). Median overall survival was 21.9 months (95% CI, 18.8-27.2) vs 19.3 months (95% CI, 16.3-22.8; P = .23). Treatment was stopped due to toxicity in 8.5% of FOLFIRI patients vs 16.5% of IROX patients, and 60-day mortality was 6.3% and 4.2% (FOLFIRI vs IROX). "We are happy that the toxicity is not worse, but to use such treatment requires experience," Dr. Schalhorn revealed. The researchers concluded that FOLFIRI and IROX had comparable toxicity but that delayed diarrhea, neurotoxicity, leukopenia, and thrombocytopenia were significantly more frequent in the IROX arm. "Normally, there is no indication to use IROX rather than FOLFIRI unless there is some contraindication to the use of 5-FU, such as congestive heart disease or problems in 5-FU metabolism. IROX works well for patients in good general condition with high motivation, but this regimen is not for patients in poor condition with poor motivation," Dr. Schalhorn said.