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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).

Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V - Br. J. Cancer (2006)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion, Crete 71110, Greece. georgsec@med.uoc.gr

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.

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Kaplan–Meier overall survival of patients treated with FOLFIRI and FOLFOXIRI.
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fig3: Kaplan–Meier overall survival of patients treated with FOLFIRI and FOLFOXIRI.

Mentions: Randomisation was performed using a minimisation technique (Pocock and Simon, 1975), stratifying patients by centre, prior adjuvant chemotherapy (yes or not) and ECOG performance status (0–1 vs 2). The primary end point of the study was OS. Secondary end points were TTP, RR and tolerance. The study was designed for two sided log-rank test to have 80% power to detect a 25% improvement in survival for the experimental arm, based on the assumption that OS would be 17 months in the standard arm (FORFIRI) (Douillard et al, 2000) and 22.5 months for the experimental arm (FOLFOXIRI) (Souglakos et al, 2002) (type I error 5%, type II error 20%). Using the Freedman's formula, 136 patients per arm were required with the assumption that the accrual period would last 48 months (Freedman, 1982). An interim analysis using O'Brien–Fleming boundaries after 50% of patients progressed was planned (O'Brien and Fleming, 1979). The Kaplan–Meier method was used to estimate survival and PFS curves, and the log-rank test was used to compare the curves (Kaplan and Meier, 1958). Cox's proportional hazards modelling was used to calculate hazard ratios (HR) and confidence intervals (CIs;) (Cox, 1972). χ2 tests were used to compare toxicity and confirmed RR. P-values <0.05 were considered statistically significant for all comparisons. All randomised patients were included in an intention-to-treat analysis; patients who canceled before the initiation of therapy were excluded from toxicity analyses (Figures 2 and 3).


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).

Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D, Georgoulias V - Br. J. Cancer (2006)

Kaplan–Meier overall survival of patients treated with FOLFIRI and FOLFOXIRI.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361370&req=5

fig3: Kaplan–Meier overall survival of patients treated with FOLFIRI and FOLFOXIRI.
Mentions: Randomisation was performed using a minimisation technique (Pocock and Simon, 1975), stratifying patients by centre, prior adjuvant chemotherapy (yes or not) and ECOG performance status (0–1 vs 2). The primary end point of the study was OS. Secondary end points were TTP, RR and tolerance. The study was designed for two sided log-rank test to have 80% power to detect a 25% improvement in survival for the experimental arm, based on the assumption that OS would be 17 months in the standard arm (FORFIRI) (Douillard et al, 2000) and 22.5 months for the experimental arm (FOLFOXIRI) (Souglakos et al, 2002) (type I error 5%, type II error 20%). Using the Freedman's formula, 136 patients per arm were required with the assumption that the accrual period would last 48 months (Freedman, 1982). An interim analysis using O'Brien–Fleming boundaries after 50% of patients progressed was planned (O'Brien and Fleming, 1979). The Kaplan–Meier method was used to estimate survival and PFS curves, and the log-rank test was used to compare the curves (Kaplan and Meier, 1958). Cox's proportional hazards modelling was used to calculate hazard ratios (HR) and confidence intervals (CIs;) (Cox, 1972). χ2 tests were used to compare toxicity and confirmed RR. P-values <0.05 were considered statistically significant for all comparisons. All randomised patients were included in an intention-to-treat analysis; patients who canceled before the initiation of therapy were excluded from toxicity analyses (Figures 2 and 3).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion, Crete 71110, Greece. georgsec@med.uoc.gr

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.

Show MeSH
Related in: MedlinePlus