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The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer.
MedLine Citation:
PMID:  24423320     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Context: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis in need of more effective treatment options. Published evidence indicates many ACCs express the vascular endothelial growth factor receptor (VEGFR), suggesting inhibiting VEGF signaling could potentially impact tumor growth. Objective: Determine the anti-tumor efficacy of axitinib (AG-013736), a potent, selective inhibitor of VEGFR1, 2, or 3. Design: Phase II, open label trial using a two-stage design. Patients: Thirteen patients with metastatic ACC previously treated with at least one chemotherapy regimen with or without mitotane. Intervention: Starting axitinib dose was 5 mg orally twice daily. Dose escalations were permitted if the administered dose was tolerable. Results: Thirteen patients were enrolled. Dose escalation was possible in seven patients, but the majority could not tolerate a dose higher than the starting 5 mg twice-daily dose for prolonged periods of time. All patients experienced known grade 1/2 toxicities and ten of thirteen had at least one grade 3/4 adverse event. No patient tumor could be scored as a RECIST response, although the growth rate on therapy compared to that prior to starting axitinib was reduced in four of the thirteen patients. The median progression-free survival was 5.48 months; the median overall survival was >13.7 months. Conclusion: Axitinib has limited effectiveness in ACC. Together with forty-eight patients previously reported that received either sorafenib or sunitinib, a total of sixty-one ACC patients have now been treated with a VEGFR tyrosine kinase inhibitor without an objective RECIST response. Future trials in ACC should look to other targets for possible active agents.
Authors:
Ciara O'Sullivan; Maureen Edgerly; Margarita Velarde; Julia Wilkerson; Aradhana M Venkatesan; Stefania Pittaluga; Sherry X Yang; Dat Nguyen; Sanjeeve Balasubramaniam; Tito Fojo
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-1
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  jc20132298     Citation Subset:  -    
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