Triplet (FOLFOXIRI) Versus Doublet (FOLFOX or FOLFIRI) Regimen as First Line Treatment in Metastatic Colorectal Carcinoma, a Prospective Phase II, Randomized Controlled Trial

BACKGROUND: The outcomes of treatment of metastatic colorectal cancer (mCRC) is still unsatisfactory. Several trials approved that, the upfront treatment with triplet regimen included fluorouracil, leucovorin, irinotecan and oxaliplatin improved the outcomes of patients with metastatic disease as compared to standard doublet regimen. The objective of our study is evaluating the impact of upfront treatment with triplet (FOLFOXIRI) regimen on both oncological outcomes (response rate and survival) and patients' tolerability in comparison to the standard doublet regimen. METHODS: We randomly enrolled 64 patients with a newly diagnosed unresectable mCRC to receive either FOLFOXIRI (experimental arm) or FOLFIRI or FOLFOX4 (control arm) biweekly up to 12 cycles. The primary endpoints are overall response rate (RR) and patients' tolerability. The secondary endpoints are the progression free and overall survival. RESULT: There was a significantly increase in RR (59% vs 37%) and complete remission rate (CR) (6.3% and 3.1%, respectively (P = 0.045) for the triplet therapy group compared to control group. Consequently, an increased rate of secondary resection of metastasis (21.9% vs 3.1% respectively; P=0.023). The FOLFOXIRI regimen was associated with higher rate of grade 3/4 toxicity but not statistically significant except febrile neutropenia (6.2%; P=0.03). There was numerical prolongation in the median PFS in the FOLFOXIRI group on compared to control group but not significantly (9 versus 8 months; P=0.11). The median OS was 20 and 22 months in FOLFOXIRI arm and control arm respectively with no statistically significant difference (P=0.57). CONCLUSION: FOLFOXIRI had a higher efficacy and higher conversion rate to secondary resection over the doublet regimen as an upfront treatment option, coupled with a manageable adverse event, but failed to improve the survival outcomes.