Rapid Decrease in Delivery of Chemotherapy to Tumors After anti-VEGF Therapy: Implications for Scheduling of Anti-Angiogenic Drugs

Cancer Cell. 2012 Jan 17;21(1):82-91. doi: 10.1016/j.ccr.2011.11.023.

Abstract

Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in cancer patients. It is assumed that anti-angiogenic drugs, such as bevacizumab, transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy. To investigate this concept, a study was performed in non-small cell lung cancer (NSCLC) patients using positron emission tomography (PET) and radiolabeled docetaxel ([(11)C]docetaxel). In NSCLC, bevacizumab reduced both perfusion and net influx rate of [(11)C]docetaxel within 5 hr. These effects persisted after 4 days. The clinical relevance of these findings is notable, as there was no evidence for a substantial improvement in drug delivery to tumors. These findings highlight the importance of drug scheduling and advocate further studies to optimize scheduling of anti-angiogenic drugs.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols*
  • Bevacizumab
  • Bone Marrow / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Docetaxel
  • Drug Administration Schedule
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy
  • Positron-Emission Tomography
  • Taxoids / administration & dosage
  • Taxoids / pharmacokinetics*
  • Taxoids / therapeutic use
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Taxoids
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Docetaxel
  • Bevacizumab