Document Detail


Reduction in skin microvascular density and changes in vessel morphology in patients treated with sunitinib.
MedLine Citation:
PMID:  20051825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypertension is a common side effect in cancer patients treated with inhibitors of vascular endothelial growth factor/vascular endothelial growth factor receptor-2 signaling and may represent a marker of clinical benefit. Functional rarefaction (a decrease in perfused microvessels) or structural rarefaction (a reduction in anatomic capillary density) may play an important role in the development of hypertension. We investigated whether sunitinib caused impairment of microvascular function and/or reduction of capillary density in patients with metastatic renal cell cancer (mRCC). Sixteen mRCC patients were treated with sunitinib (50 mg/day). Assessments of 24-h ambulatory blood pressure, microvascular endothelial function by laser Doppler fluxmetry, and capillary density by capillary microscopy were performed at baseline and days 14 and 28. Median blood pressure had increased on day 14 (systolic 10 mmHg, P<0.01 and diastolic blood pressure 8 mmHg, P<0.01). Capillary density had decreased from 69 to 61 capillaries/mm (P<0.01). This decrease was related to the increase in systolic and diastolic blood pressure (r=-0.57, P<0.05 and r=-0.68, P<0.01, respectively). A more pronounced decrease in capillary density was associated with increased visibility of the subpapillary plexus (P=0.041). Preliminary findings indicated that median progression-free survival was significantly prolonged in patients with a greater than 6 capillaries/mm decrease in density as compared with patients with a less pronounced decrease (P=0.044). In conclusion, reduction in skin capillary density is associated with a rise in blood pressure during sunitinib therapy and, by itself, might be useful as a predictive marker of clinical outcome.
Authors:
Astrid A M van der Veldt; Michiel P de Boer; Epie Boven; Etto C Eringa; Alfons J M van den Eertwegh; Victor W van Hinsbergh; Yvo M Smulders; Erik H Sern?
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  21     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-10     Completed Date:  2010-06-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  439-46     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors / adverse effects*,  therapeutic use
Capillaries / anatomy & histology,  drug effects*,  physiopathology
Female
Humans
Hypertension / chemically induced
Indoles / adverse effects*,  therapeutic use
Kidney Neoplasms / drug therapy
Male
Middle Aged
Pyrroles / adverse effects*,  therapeutic use
Skin / blood supply*,  drug effects,  physiopathology
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Indoles; 0/Pyrroles; 0/sunitinib

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