title: Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.
abstract: Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs.
  
  
  
  A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design.
  
  
  
  The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I2= 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months.
  
  
  
  Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting.
authors.affiliation: Department of Medical Oncology, Nepean Cancer Care Centre, Sydney, New South Wales, Australia.
authors.forename: Dhanusha
authors.initials: D
authors.lastname: Sabanathan
authors.affiliation: Discipline of Surgery, Whiteley-Martin Research Centre, University of Sydney, Sydney Medical School, Sydney, New South Wales, Australia. Electronic address: eslickg@med.usyd.edu.au.
authors.forename: Guy D
authors.initials: GD
authors.lastname: Eslick
authors.affiliation: Department of Medical Oncology, Nepean Cancer Care Centre, Sydney, New South Wales, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Shannon
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D020360:Neoadjuvant Therapy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents
keywords: Adjuvant therapy; Combination therapy; Liver resection; Metastatic colorectal cancer; Surgery