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)

Abstract

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-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m−2) was given on d1, L-OHP (65 mg m−2) on d2, LV (200 mg m−2) on days 2 and 3 and 5-FU (400 mg m−2 as i.v. bolus and 600 mg m−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.

BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients’ outcome

“…The majority of patients were treated in the context of two clinical trials conducted at our centre (Souglakos et al, 2006;Emmanouilides et al, 2007; Tables 1 and 2). Patients were evaluated at baseline and every four cycles of chemotherapy.…”

Current role of antibody therapy in patients with metastatic colorectal cancer

“…Thus it seems as if the improvement in OS has reached a limit of around 18-21 months and even if all patients are exposed to all three drugs, either sequentially or concomitantly, it is not expected that the OS can be prolonged beyond 24 months Falcone et al, 2006;Souglakos et al, 2006).…”

Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic colorectal cancer: a Phase I study

“…Souglakos et al (2006) reported a 57% response rate when irinotecan and oxaliplatin were given 'up front' with 5-FU to a cohort of 57 patients. Falcone et al (2002) reported a higher response rate (71%) using a similar combination, as well as a 26.5-month overall survival and a 10.4-month PFS, which was comparable with the 8.8 months observed in our study.…”

“…One way forward, therefore, might be to combine a fluoropyrimidine with both oxaliplatin and irinotecan in the first-line setting so that a patient receives all three drugs 'up front'. Previous studies of irinotecan and oxaliplatin with 5-FU have reported high response rates and impressive survival times (Falcone et al, 2002;Souglakos et al, 2006), suggesting that further investigation of concurrent administration of all three drugs is warranted in the first-line management of patients with metastatic colorectal cancer.…”