Masahiro Sugawara1, David L Geffner, Dorothy Martinez, Jerome M Hershman. 1. Endocrinology and Diabetes Division, Veterans Affairs Greater Los Angeles Medical Center, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. msugawar@ucla.edu
Abstract
PURPOSE OF REVIEW: Metastatic medullary thyroid cancer (MTC) is an incurable disease once metastasis becomes unresectable. Many therapeutic drugs and methods have been tried to circumvent this difficulty. We review currently published treatments and hope for future developments of more effective treatment methods. RECENT FINDINGS: Motesanib, vandetanib, axitinib (tyrosine kinase inhibitors), and XL184 (multikinase inhibitor) have been shown to achieve partial response or stable disease state of metastatic MTC. Sunitinib and sorafenib, currently available tyrosine kinase inhibitors, can also be tried for patients with MTC. However, these medications are not curative and do not improve survival rate. Only carcinoembryonic antigen-I-iodine-based radioimmunotherapy improved survival of a subset of patients with a very aggressive type of MTC. Drugs currently available for possible use of MTC treatment include bortezomib (proteasome inhibitor), valproic acid (histone deacetylase inhibitor), capecitabine (5-fluorouracil prodrug), and indomethacin (NSAID), although clinical studies have yet to be done. Cardiac natriuretic hormones and an extract of the plant Cautleya gracilis are new agents to be studied for MTC. SUMMARY: Kinase inhibitors are the first drugs showing some efficacy in MTC. To improve survival, unconventional drugs or other therapies with or without kinase inhibitors need to be considered.
PURPOSE OF REVIEW: Metastatic medullary thyroid cancer (MTC) is an incurable disease once metastasis becomes unresectable. Many therapeutic drugs and methods have been tried to circumvent this difficulty. We review currently published treatments and hope for future developments of more effective treatment methods. RECENT FINDINGS:Motesanib, vandetanib, axitinib (tyrosine kinase inhibitors), and XL184 (multikinase inhibitor) have been shown to achieve partial response or stable disease state of metastatic MTC. Sunitinib and sorafenib, currently available tyrosine kinase inhibitors, can also be tried for patients with MTC. However, these medications are not curative and do not improve survival rate. Only carcinoembryonic antigen-I-iodine-based radioimmunotherapy improved survival of a subset of patients with a very aggressive type of MTC. Drugs currently available for possible use of MTC treatment include bortezomib (proteasome inhibitor), valproic acid (histone deacetylase inhibitor), capecitabine (5-fluorouracil prodrug), and indomethacin (NSAID), although clinical studies have yet to be done. Cardiac natriuretic hormones and an extract of the plant Cautleya gracilis are new agents to be studied for MTC. SUMMARY: Kinase inhibitors are the first drugs showing some efficacy in MTC. To improve survival, unconventional drugs or other therapies with or without kinase inhibitors need to be considered.