Frederico Leal1, Fernanda Proa Ferreira1, Andre Deeke Sasse2. 1. Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil. 2. Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil. Electronic address: sasse@cevon.com.br.
Abstract
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases. Studies reporting results from prospective, randomized clinical trials comparing FOLFOXIRI to less aggressive regimens for treatment of mCRC were selected for meta-analysis. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were the outcomes of interest. The pooled hazard ratio (HR) and pooled odds ratio (OR) was calculated for the time-to-event endpoints and dichotomous endpoints, respectively. RESULTS: Four studies were included in the final analysis. The pooled data showed a significant benefit favoring FOLFOXIRI in terms of OS (HR, 0.80; 95% confidence interval [CI], 0.70-0.92), PFS (HR, 0.68; 95% CI, 0.55-0.85), and ORR (OR, 1.9; 95% CI, 1.36-2.67). Toxicity was significantly greater in the FOLFOXIRI arm. Heterogeneity across trials and risk of publication bias were low. CONCLUSION: FOLFOXIRI provides superior outcomes for mCRC compared with standard chemotherapy regimens. The toxicity is greater with FOLFOXIRI but manageable. The role of targeted agents combined with FOLFOXIRI is uncertain, and further research is warranted.
INTRODUCTION:Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases. Studies reporting results from prospective, randomized clinical trials comparing FOLFOXIRI to less aggressive regimens for treatment of mCRC were selected for meta-analysis. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and toxicity were the outcomes of interest. The pooled hazard ratio (HR) and pooled odds ratio (OR) was calculated for the time-to-event endpoints and dichotomous endpoints, respectively. RESULTS: Four studies were included in the final analysis. The pooled data showed a significant benefit favoring FOLFOXIRI in terms of OS (HR, 0.80; 95% confidence interval [CI], 0.70-0.92), PFS (HR, 0.68; 95% CI, 0.55-0.85), and ORR (OR, 1.9; 95% CI, 1.36-2.67). Toxicity was significantly greater in the FOLFOXIRI arm. Heterogeneity across trials and risk of publication bias were low. CONCLUSION:FOLFOXIRI provides superior outcomes for mCRC compared with standard chemotherapy regimens. The toxicity is greater with FOLFOXIRI but manageable. The role of targeted agents combined with FOLFOXIRI is uncertain, and further research is warranted.