A review of the evolution of systemic chemotherapy in the management of colorectal cancer

Clin Colorectal Cancer. 2015 Mar;14(1):1-10. doi: 10.1016/j.clcc.2014.11.002. Epub 2014 Nov 15.

Abstract

Herein we present a historical review of the development of systemic chemotherapy for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in 1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and the advent of novel cytotoxic agents, including the topoisomerase I inhibitor irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin) and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in overall survival times of approximately 2 years. When used as adjuvant therapy, FOLFOX also improves survival and is now the gold standard of care in this setting. Biological agents have been discovered that enhance the effect of cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that targets vascular endothelial growth factor, a central regulator of angiogenesis) and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal growth factor receptor). Despite the ongoing development of novel antitumor agents and therapeutic principles as we enter the era of personalized cancer medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to be the cornerstone of treatment for patients with CRC.

Keywords: 5,10-Methylenetetrahydrofolate; 5-Fluorouracil; FOLFIRI; FOLFOX; Leucovorin.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Design*
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Molecular Targeted Therapy

Substances

  • Antibodies, Monoclonal
  • Leucovorin
  • Fluorouracil