title: Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: implications for scheduling of anti-angiogenic drugs.
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.
authors.affiliation: Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands. aam.vanderveldt@vumc.nl
authors.forename: Astrid A M
authors.initials: AA
authors.lastname: Van der Veldt
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Idris
authors.initials: I
authors.lastname: Bahce
authors.forename: Maudy
authors.initials: M
authors.lastname: Walraven
authors.forename: Michiel P
authors.initials: MP
authors.lastname: de Boer
authors.forename: Henri N J M
authors.initials: HN
authors.lastname: Greuter
authors.forename: N Harry
authors.initials: NH
authors.lastname: Hendrikse
authors.forename: Jonas
authors.initials: J
authors.lastname: Eriksson
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Henk M
authors.initials: HM
authors.lastname: Verheul
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D001853:Bone Marrow / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D049268:Positron-Emission Tomography; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D000068258:Bevacizumab