Document Detail


Pilot trial of sunitinib therapy in patients with von Hippel-Lindau disease.
MedLine Citation:
PMID:  22105611     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Von Hippel-Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluated the safety and efficacy of sunitinib in VHL patients and examined the expression of candidate receptors in archived tissue.
METHODS: Patients with VHL were given four cycles of 50 mg sunitinib daily for 28 days, followed by 14 days off. Primary end point was toxicity. Modified RECIST were used for efficacy assessment. We evaluated 20 archival renal cell carcinomas (RCCs) and 20 hemangioblastomas (HBs) for biomarker expression levels using laser-scanning cytometry (LSC).
RESULTS: Fifteen patients were treated. Grade 3 toxicity included fatigue in five patients. Dose reductions were needed in 10 patients. Eighteen RCC and 21 HB lesions were evaluable. Six of the RCCs (33%) responded partially, versus none of the HBs (P = 0.014). LSC revealed that mean levels of phosphorylated vascular endothelial growth factor receptor-2 were lower in HB than in RCC endothelium (P = 0.003) and mean phosphorylated fibroblast growth factor receptor substrate-2 (pFRS2) levels were higher in HB (P = 0.003).
CONCLUSIONS: Sunitinib treatment in VHL patients showed acceptable toxicity. Significant response was observed in RCC but not in HB. Greater expression of pFRS2 in HB tissue than in RCC raises the hypothesis that treatment with fibroblast growth factor pathway-blocking agents may benefit patients with HB.
Authors:
E Jonasch; I E McCutcheon; S G Waguespack; S Wen; D W Davis; L A Smith; N M Tannir; D S Gombos; G N Fuller; S F Matin
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  22     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-22     Completed Date:  2012-03-16     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2661-6     Citation Subset:  IM    
Affiliation:
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. ejonasch@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Antineoplastic Agents / adverse effects,  therapeutic use*
Carcinoma, Renal Cell / drug therapy,  metabolism
Female
Hemangioblastoma / drug therapy,  metabolism
Humans
Indoles / adverse effects,  therapeutic use*
Kidney Neoplasms / drug therapy,  metabolism
Male
Middle Aged
Neuroendocrine Tumors / drug therapy,  radiography
Pancreatic Neoplasms / drug therapy,  radiography
Pilot Projects
Pyrroles / adverse effects,  therapeutic use*
Treatment Outcome
Young Adult
von Hippel-Lindau Disease / drug therapy*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Indoles; 0/Pyrroles; 0/sunitinib
Comments/Corrections
Comment In:
Eur Urol. 2013 Apr;63(4):770   [PMID:  23438395 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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