Medullary thyroid cancer medical therapy: Difference between revisions
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[[Cabozantinib]], trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication.<ref>{{cite web|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm330143.htm|title=FDA approves Cometriq to treat rare type of thyroid cancer|accessdate= 29 November 2012}}</ref> Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg. | [[Cabozantinib]], trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication.<ref>{{cite web|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm330143.htm|title=FDA approves Cometriq to treat rare type of thyroid cancer|accessdate= 29 November 2012}}</ref> Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg. | ||
===Radiation=== | |||
[[External beam radiotherapy]] is recommended when there is a high risk of regional recurrence, even after optimum surgical treatment.<ref name=NCCN /><ref name="pmid8875751">{{cite journal |author=Brierley J, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T|title=Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control |journal=Thyroid |volume=6 |issue=4 |pages=305–10 |year=1996 |pmid=8875751 |doi=10.1089/thy.1996.6.305}}</ref> In this study, patients treated with external beam radiation were compared to a control group. Disease control with radiation was far superior in the group receiving radiation. The authors of the study [14] wrote: "in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse." | |||
Unlike other differentiated thyroid carcinoma, there is no role for [[radioiodine]] treatment in medullary-type disease.<ref name="pmid15719378">{{cite journal |author=Quayle FJ, Moley JF |title=Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes |journal=J Surg Oncol |volume=89 |issue=3 |pages=122–9 |year=2005 |pmid=15719378 |doi=10.1002/jso.20184}}</ref> | |||
==Reference== | ==Reference== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Medical Therapy
Protein kinase inhibitors
Clinical trials of protein kinase inhibitors,[1] which block the abnormal kinase proteins involved in the development and growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority of responders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responses have been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension, nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.
Vandetanib, trade name Caprelsa, was the first drug (April 2011) to be approved by US Food and Drug Administration (FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.[2]
Cabozantinib, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication.[3] Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg.
Radiation
External beam radiotherapy is recommended when there is a high risk of regional recurrence, even after optimum surgical treatment.[4][5] In this study, patients treated with external beam radiation were compared to a control group. Disease control with radiation was far superior in the group receiving radiation. The authors of the study [14] wrote: "in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse."
Unlike other differentiated thyroid carcinoma, there is no role for radioiodine treatment in medullary-type disease.[6]
Reference
- ↑ "American Thyroid Association - Thyroid Clinical Trials". Retrieved 2007-12-21.
- ↑ "FDA approves new treatment for rare form of thyroid cancer". Retrieved 7 April 2011.
- ↑ "FDA approves Cometriq to treat rare type of thyroid cancer". Retrieved 29 November 2012.
- ↑
- ↑ Brierley J, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T (1996). "Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control". Thyroid. 6 (4): 305–10. doi:10.1089/thy.1996.6.305. PMID 8875751.
- ↑ Quayle FJ, Moley JF (2005). "Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes". J Surg Oncol. 89 (3): 122–9. doi:10.1002/jso.20184. PMID 15719378.