FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC):: a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin ( L-OHP) in combination with irinotecan ( CPT-11), 5- fluorouracil (5-FU) and leucovorin ( LV) ( FOLFOXIRI) vs irinotecan and 5- FU/ LV ( FOLFIRI) as first- line treatment of patients with metastatic colorectal cancer ( MCC). A total of 283 chemotherapy- naive patients with MCC were enrolled ( FOLFIRI arm: n = 146; FOLFOXIRI arm: n = 137). In the FOLFOXIRI arm, CPT-11 ( 150 mgm(-2)) was given on d(1), L-OHP ( 65 mgm(-2)) on d(2), LV ( 200 mgm(-2)) on days 2 and 3 and 5-FU ( 400 mg m(-2) as i. v. bolus and 600 mgm(-2) as 22 h i. v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 ( 180 mg m(-2)) was given on d1 whereas LV and 5- FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival ( median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P= 0.337), median time to disease progression ( FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P= 0.17), response rates ( 33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P= 0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia ( P= 0.0001), diarrhoea ( P= 0.0001) and neurosensory toxicity ( P 0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature.