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The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer. | LitMetric

The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer.

J Clin Endocrinol Metab

Medical Oncology Branch (C.O., M.E., M.V., J.W., S.B., T.F.), Center for Cancer Research, Laboratory of Pathology (S.P.), and National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis (S.X.Y., D.N.), National Cancer Institute, and Radiology and Imaging Sciences (A.M.V.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892.

Published: April 2014

AI Article Synopsis

Article Abstract

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 vascular endothelial growth factor signaling could potentially impact tumor growth.

Objective: The objective of the study was to determine the antitumor efficacy of axitinib (AG-013736), a potent, selective inhibitor of VEGFR1, -2, and -3.

Design: This was a 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 participated in the study.

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 10 of 13 patients had at least one grade 3/4 adverse event. No patient tumor could be scored as a Response Evaluation Criteria in Solid Tumors response, although the growth rate on therapy compared with that prior to starting axitinib was reduced in 4 of the 13 patients. The median progression-free survival was 5.48 months, and the median overall survival was longer than 13.7 months.

Conclusion: Axitinib has limited effectiveness in ACC. Together with 48 patients previously reported who received either sorafenib or sunitinib, a total of 61 ACC patients have now been treated with a VEGFR tyrosine kinase inhibitor without an objective Response Evaluation Criteria in Solid Tumors response. Future trials in ACC should look to other targets for possible active agents.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973787PMC
http://dx.doi.org/10.1210/jc.2013-2298DOI Listing

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