title: Survival benefit and safety of the combinations of FOLFOXIRI ± bevacizumab versus the combinations of FOLFIRI ± bevacizumab as first-line treatment for unresectable metastatic colorectal cancer: a meta-analysis.
abstract: BACKGROUND
  The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%-80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC.
  
  
  METHODS
  PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included.
  
  
  RESULTS
  Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73-0.97), progression-free survival (HR, 0.69; 95% CI, 0.59-0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28-2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm.
  
  
  CONCLUSIONS
  Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population.
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing; Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu.
authors.forename: Meng
authors.initials: M
authors.lastname: Kuang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Nanjing Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Cuiju
authors.initials: C
authors.lastname: Tang
keywords: FOLFIRI; FOLFOXIRI; chemotherapy; colorectal cancer; meta-analysis