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

August 1, 2005

MUNICH, GERMANY-Irinotecan(Camptosar) plus fluorouracil(5-FU)/folinic acid (FOLFIRI) issignificantly better at controlling

MUNICH, GERMANY-Irinotecan(Camptosar) plus fluorouracil(5-FU)/folinic acid (FOLFIRI) issignificantly better at controllingmetastatic colorectal cancer (CRC) thanirinotecan/oxaliplatin (Eloxatin)(IROX)and should be the preferred first-linetreatment, Andreas Schalhorn, MD, ofKlin Grosshadern in Munich, said (abstract3516). Delayed toxicity rates alsofavored FOLFIRI.FIRE TrialDr. Schalhorn reported the FIREtrial, a phase III randomized crossoverstudy that compared the first-line efficacyand toxicity of infusional 5-FU/FA (the AIO regimen) plus irinotecan(FOLFIRI) with IROX.The study enrolled 488 patientsfrom 56 centers between July 2000and September 2004. Patients in theFOLFIRI arm received folinic acid (500mg/m2) plus 5-FU (2,000 mg/m2 as a24-hour infusion) plus irinotecan (80mg/m2 given weekly for 6 weeks). Patientsin the IROX arm were treatedwith oxaliplatin (85 mg/m2 on days 1,15, and 29) and irinotecan (80 mg/m2)weekly for 6 weeks. Treatment cycleswere repeated on day 50 in both treatmentarms. The primary endpoint wasprogression-free survival, and patientswere allowed to cross over to the comparatorregimen at disease progression.Dr. Schalhorn presented efficacydata for 299 patients (157 FOLFIRI,142 IROX). The complete remissionrate was 8% in both arms. The partialremission rate was 37% with FOLFIRIvs 40% with IROX, for an overall remissionrate of 45% vs 48% (P = nonsignificant).Stable disease was documented in44% of FOLFIRI patients vs 31% ofIROX patients (P =.004), resulting ina disease control rate of 89% vs 79%(P = .004).Improvement in SurvivalMedian progression-free survivalwas 8.2 months with FOLFIRI (95%confidence interval [CI], 7.3-9.6) vs7.0 months with IROX (95% CI, 6.4-8.2; P = .15). Median overall survivalwas 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 toxicityin 8.5% of FOLFIRI patients vs16.5% of IROX patients, and 60-daymortality was 6.3% and 4.2% (FOLFIRIvs IROX)."We are happy that the toxicity isnot worse, but to use such treatmentrequires experience," Dr. Schalhornrevealed.The researchers concluded thatFOLFIRI and IROX had comparabletoxicity but that delayed diarrhea, neurotoxicity,leukopenia, and thrombocytopeniawere significantly more frequentin the IROX arm."Normally, there is no indicationto use IROX rather than FOLFIRIunless there is some contraindicationto the use of 5-FU, such as congestiveheart disease or problems in 5-FUmetabolism. IROX works well forpatients in good general condition withhigh motivation, but this regimenis not for patients in poor conditionwith poor motivation," Dr. Schalhornsaid.