XL184 (cabozantinib) for medullary thyroid carcinoma

Introduction: Intrathyroidal medullary thyroid carcinoma (MTC) can generally be cured by surgery, but distant metastases are often already present at diagnosis. Currently, there is no effective treatment for metastatic MTC. In these cases, consensus treatment guidelines explicitly recommend new experimental drugs. Several kinase inhibitors are now being tested for treatment of MTC in clinical trials and XL184, an oral, small-molecule multi-kinase inhibitor, seems to be one of the most promising of these compounds. Areas covered: We review preliminary data on the safety and efficacy of XL184 in metastatic MTC based on an extensive search of the literature, which included published articles, abstracts and website information. In particular, the review focuses on the rationale for using XL184 in advanced MTC. The compound has been specifically designed to target multiple signaling pathways, and this is expected to produce synergistic antitumor effects superior to those achieved by single-kinase inhibition. Preliminary results from the Phase I study of XL184 seem to support this hypothesis. Expert opinion: Multiple receptor tyrosine kinases (RTKs) are concomitantly activated in the same tumor. The blockade of a single RTK may engage compensatory signaling that maintains cell growth. Targeting multiple kinases might overcome both intrinsic and acquired resistance to antitumoral drugs.