title: Adjuvant treatment of colon cancer: what is next?
abstract: OBJECTIVE
  Since 2003, fluorouracil/leucovorin plus oxaliplatin (FOLFOX) has been the standard of care in adjuvant therapy. This review reports the results of recent phase III trials which have attempted to improve upon the existing standard of care in adjuvant therapy. In addition, we examine how results of these trials have shaped our knowledge and outline directions for future research.
  
  
  RESULTS
  The demonstrated efficacy of adding irinotecan, bevacizumab, or cetuximab to fluorouracil-based regimens in the treatment of patients with metastatic colorectal cancer led to several multicenter phase III trials investigating the efficacy of these agents in the adjuvant setting. In the last 2 years, all of these trials have reported failures to improve patient outcomes, and the field has remained essentially static.
  
  
  CONCLUSIONS
  Negative results from multiple phase III trials suggest that the existing paradigm for the selection of agents to use in adjuvant trials is deeply flawed. Moving forward, we need to ensure mechanistic rationale for clinical trial design and reassess whether disease-free survival is the primary endpoint that should be used to evaluate biologic agents. Future research should be directed toward the development of prognostic and predictive markers for the development of a data-driven roadmap to inform risk stratification and therapeutic decision-making.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, California 94115, USA. katherine.vanloon@ucsf.edu
authors.forename: Katherine
authors.initials: K
authors.lastname: Van Loon
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077146:Irinotecan; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin