Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs

Astrid A M Van der Veldt; Mark Lubberink; Idris Bahce; Maudy Walraven; Michiel P de Boer; Henri N J M Greuter; N Harry Hendrikse; Jonas Eriksson; Albert D Windhorst; Pieter E Postmus; Henk M Verheul; Erik H Serné; Adriaan A Lammertsma; Egbert F Smit

doi:10.1016/j.ccr.2011.11.023

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.

Authors

Astrid A M Van der Veldt¹, Mark Lubberink, Idris Bahce, Maudy Walraven, Michiel P de Boer, Henri N J M Greuter, N Harry Hendrikse, Jonas Eriksson, Albert D Windhorst, Pieter E Postmus, Henk M Verheul, Erik H Serné, Adriaan A Lammertsma, Egbert F Smit

Affiliation

¹ Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands. aam.vanderveldt@vumc.nl

PMID: 22264790
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