Show simple item record

dc.contributor.authorJayson, Gordon C
dc.contributor.authorParker, Geoff J M
dc.contributor.authorMullamitha, Saifee A
dc.contributor.authorValle, Juan W
dc.contributor.authorSaunders, Mark P
dc.contributor.authorBroughton, Lynn
dc.contributor.authorLawrance, Jeremy A L
dc.contributor.authorCarrington, Bernadette M
dc.contributor.authorRoberts, Caleb
dc.contributor.authorIssa, B
dc.contributor.authorBuckley, David L
dc.contributor.authorCheung, Susan
dc.contributor.authorDavies, Karen
dc.contributor.authorWatson, Yvonne
dc.contributor.authorZinkewich-Peotti, K
dc.contributor.authorRolfe, L
dc.contributor.authorJackson, A
dc.date.accessioned2009-08-10T17:08:46Z
dc.date.available2009-08-10T17:08:46Z
dc.date.issued2005-02-10
dc.identifier.citationBlockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab', leads to fluid accumulation and is associated with increased tumor vascularized volume. 2005, 23 (5):973-81 J. Clin. Oncol.en
dc.identifier.issn0732-183X
dc.identifier.pmid15466784
dc.identifier.doi10.1200/JCO.2005.01.032
dc.identifier.urihttp://hdl.handle.net/10541/76827
dc.description.abstractPURPOSE: CDP860 is an engineered Fab' fragment-polyethylene glycol conjugate, which binds to and blocks the activity of the beta-subunit of the platelet-derived growth factor receptor (PDGFR-beta). Studies in animals have suggested that PDGFR-beta inhibition reduces tumor interstitial fluid pressure, and thus increases the uptake of concomitantly administered drugs. The purpose of this study was to determine whether changes in tumor vascular parameters could be detected in humans, and to assess whether CDP860 would be likely to increase the uptake of a concurrently administered small molecule in future studies. PATIENTS AND METHODS: Patients with advanced ovarian or colorectal cancer and good performance status received intravenous infusions of CDP860 on days 0 and 28. Patients had serial dynamic contrast-enhanced magnetic resonance imaging studies to measure changes in tumor vascular parameters. RESULTS: Three of eight patients developed significant ascites, and seven of eight showed evidence of fluid retention. In some patients, the ratio of vascular volume to total tumor volume increased significantly (P < .001) within 24 hours following CDP860 administration, an effect suggestive of recruitment of previously non-functioning vessels. CONCLUSION: These observations suggest that inhibition of PDGFR-beta might improve delivery of a concurrently administered therapy. However, in cancer patients, further exploration of the dosing regimen of CDP860 is required to dissociate adverse effects from beneficial effects. The findings challenge the view that inhibition of PDGF alone is beneficial, and confirm that effects of PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in patients treated with mixed tyrosine kinase inhibitors.
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectOvarian Canceren
dc.subjectTumour Burdenen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAscites
dc.subject.meshCapillary Permeability
dc.subject.meshColonic Neoplasms
dc.subject.meshContrast Media
dc.subject.meshExtracellular Fluid
dc.subject.meshFemale
dc.subject.meshFollow-Up Studies
dc.subject.meshHumans
dc.subject.meshImage Processing, Computer-Assisted
dc.subject.meshImmunoglobulin Fab Fragments
dc.subject.meshMagnetic Resonance Imaging
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshOvarian Neoplasms
dc.subject.meshPleural Effusion
dc.subject.meshPolyethylene Glycols
dc.subject.meshReceptor, Platelet-Derived Growth Factor beta
dc.subject.meshRectal Neoplasms
dc.subject.meshRegional Blood Flow
dc.subject.meshTumor Burden
dc.titleBlockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab', leads to fluid accumulation and is associated with increased tumor vascularized volume.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK, Department of Medical Oncology, Christie Hospital, Manchester M20 4BX, United Kingdom. Gordon.Jayson@christie-tr.nwest.nhs.uken
dc.identifier.journalJournal of Clinical Oncologyen
html.description.abstractPURPOSE: CDP860 is an engineered Fab' fragment-polyethylene glycol conjugate, which binds to and blocks the activity of the beta-subunit of the platelet-derived growth factor receptor (PDGFR-beta). Studies in animals have suggested that PDGFR-beta inhibition reduces tumor interstitial fluid pressure, and thus increases the uptake of concomitantly administered drugs. The purpose of this study was to determine whether changes in tumor vascular parameters could be detected in humans, and to assess whether CDP860 would be likely to increase the uptake of a concurrently administered small molecule in future studies. PATIENTS AND METHODS: Patients with advanced ovarian or colorectal cancer and good performance status received intravenous infusions of CDP860 on days 0 and 28. Patients had serial dynamic contrast-enhanced magnetic resonance imaging studies to measure changes in tumor vascular parameters. RESULTS: Three of eight patients developed significant ascites, and seven of eight showed evidence of fluid retention. In some patients, the ratio of vascular volume to total tumor volume increased significantly (P < .001) within 24 hours following CDP860 administration, an effect suggestive of recruitment of previously non-functioning vessels. CONCLUSION: These observations suggest that inhibition of PDGFR-beta might improve delivery of a concurrently administered therapy. However, in cancer patients, further exploration of the dosing regimen of CDP860 is required to dissociate adverse effects from beneficial effects. The findings challenge the view that inhibition of PDGF alone is beneficial, and confirm that effects of PDGFR kinase inhibition mediate, to some extent, the fluid retention observed in patients treated with mixed tyrosine kinase inhibitors.


This item appears in the following Collection(s)

Show simple item record