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|Title:||A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H|
Morris III, J.C.
|Citation:||Bible, K.C., Suman, V.J., Molina, J.R., Smallridge, R.C., Maples, W.J., Menefee, M.E., Rubin, J., Karlin, N., Sideras, K., Morris III, J.C., McIver, B., Hay, I., Fatourechi, V., Burton, J.K., Webster, K.P., Bieber, C., Traynor, A.M., Flynn, P.J., Goh, B.C., Isham, C.R., Harris, P., Erlichman, C. (2014). A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. Journal of Clinical Endocrinology and Metabolism 99 (5) : 1687-1693. ScholarBank@NUS Repository. https://doi.org/10.1210/jc.2013-3713|
|Abstract:||Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatmentrequiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. © 2014 by the Endocrine Society.|
|Source Title:||Journal of Clinical Endocrinology and Metabolism|
|Appears in Collections:||Staff Publications|
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