title: Targeted therapies in metastatic colorectal cancer: a systematic review and assessment of currently available data.
abstract: BACKGROUND
  Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved. The aim of this review is to summarize and assess the effects of molecular agents in mCRC based on the available phase II and III trials, pooled analyses, and meta-analyses/systematic reviews.
  
  
  METHODS
  A systematic literature search was conducted using the meta-database of the German Institute of Medical Documentation and Information. Criteria of the Scottish Intercollegiate Guidelines Network were used to assess the quality of the controlled trials and systematic reviews/meta-analyses.
  
  
  RESULTS
  Of the 806 retrieved records, 40 publications were included. For bevacizumab, efficacy in combination with fluoropyrimidine-based chemotherapy in first- and subsequent-line settings has been shown. The benefit of continued VEGF targeting has also been demonstrated with aflibercept and regorafenib. Cetuximab is effective with fluoropyrimidine, leucovorin, and irinotecan (FOLFIRI) in first-line settings and as a single agent in last-line settings. Efficacy for panitumumab has been shown with oxaliplatin with fluoropyrimidine in first-line settings, with FOLFIRI in second-line settings, and as monotherapy in last-line settings. Treatment of anti-EGFR antibodies is restricted to patients with tumors that do not harbor mutations in Kirsten rat sarcoma and in neuroblastoma RAS.
  
  
  CONCLUSIONS
  Among various therapeutic options, the future challenge will be a better selection of the population that will benefit the most from specific anti-VEGF or anti- EGFR treatment and a careful consideration of therapy sequence.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Kirstein
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Lange
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Prenzler
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicka
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Leibniz University Hannover, Center for Health Economics Research Hannover, Hannover, Germany; Cancer Center Reutlingen, Reutlingen, Germany vogel.arndt@mh-hannover.de.
authors.forename: Arndt
authors.initials: A
authors.lastname: Vogel
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D058990:Molecular Targeted Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077544:Panitumumab; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Aflibercept; Bevacizumab; Cetuximab; Colorectal cancer; Panitumumab; Regorafenib