Pharmacokinetic and pharmacodynamic evaluation of aflibercept for the treatment of colorectal cancer

Enrique Sanz-Garcia, Tamara Saurí, Josep Tabernero, Teresa MacArulla

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

© 2015 Informa UK, Ltd. Introduction: Colorectal cancer (CRC) is currently one of the most lethal and prevalent tumors worldwide. Prognosis in the metastatic setting remains poor despite therapeutic advances. In addition to chemotherapy, new drugs have recently been developed targeting signaling pathways involved in tumor growth, differentiation and angiogenesis. Aflibercept, a recombinant protein derived from VEGF receptors 1 and 2, also targets this angiogenesis pathway but via a different mechanism, acting as VEGF decoy, thus blocking other VEGFs.Areas covered: A comprehensive review of preclinical studies with aflibercept in cell lines and xenografts of different tumor types is presented. Aflibercept safety, pharmacokinetics and pharmacodynamics data from Phase I studies in solid tumor patients are discussed. Implications of Phase II studies and the pivotal Phase III VELOUR trial of second-line treatment in metastatic CRC (mCRC) patients evaluating aflibercept alone or combined with chemotherapy are also described.Expert opinion: In this challenging field, aflibercept offers a good option for oxaliplatin-refractory mCRC patients when combined with irinotecan and 5-fluorouracil irrespective of prior anti-angiogenic treatment. Therapeutic management may be further advanced by characterization of patients with predictive biomarkers and molecular profiles to improve benefit with this treatment.
Original languageEnglish
Pages (from-to)995-1004
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2015

Keywords

  • Aflibercept
  • Angiogenesis
  • Metastatic colorectal cancer
  • VEGF
  • VEGF-Trap

Fingerprint

Dive into the research topics of 'Pharmacokinetic and pharmacodynamic evaluation of aflibercept for the treatment of colorectal cancer'. Together they form a unique fingerprint.

Cite this