Medullary thyroid cancer medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The predominant therapy for medullary thyroid cancer is surgical resection. Adjunctive | The predominant therapy for medullary thyroid cancer is [[surgical]] resection. Adjunctive chemo radiation may be required. The optimal therapy for medullary thyroid cancer depends on the stage at [[diagnosis]]. | ||
depends on the stage at diagnosis. | |||
==Medical Therapy== | ==Medical Therapy== | ||
===Protein kinase inhibitors=== | ===Protein kinase inhibitors=== | ||
Clinical trials of [[protein kinase inhibitor]]s,<ref name="titleAmerican Thyroid Association - Thyroid Clinical Trials">{{cite web |url=http://www.thyroidtrials.org |title=American Thyroid Association - Thyroid Clinical Trials |accessdate=2007-12-21 |format= |work=}}</ref> 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]].<ref>{{cite web|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm250168.htm|title=FDA approves new treatment for rare form of thyroid cancer|accessdate=7 April 2011}}</ref> | ||
* [[Cabozantinib]], 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> | |||
[[Vandetanib]] | *[[Cabozantinib]] which is a potent inhibitor of ''[[RET proto-oncogene|RET]]'', ''MET'' and ''[[VEGF]]'' was evaluated in a double-blind placebo controlled trial. | ||
* Clinical trials of [[protein kinase inhibitor]]s,<ref name="titleAmerican Thyroid Association - Thyroid Clinical Trials">{{cite web |url=http://www.thyroidtrials.org |title=American Thyroid Association - Thyroid Clinical Trials |accessdate=2007-12-21 |format= |work=}}</ref> 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. | |||
[[ | '''Adult''' | ||
* Preferred regimen: [[Vandetanib]] 300 mg PO daily until [[disease]] progression or unacceptable [[toxicity]].<ref name="pmid22665903">{{cite journal |vauthors=Thornton K, Kim G, Maher VE, Chattopadhyay S, Tang S, Moon YJ, Song P, Marathe A, Balakrishnan S, Zhu H, Garnett C, Liu Q, Booth B, Gehrke B, Dorsam R, Verbois L, Ghosh D, Wilson W, Duan J, Sarker H, Miksinski SP, Skarupa L, Ibrahim A, Justice R, Murgo A, Pazdur R |title=Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary |journal=Clin. Cancer Res. |volume=18 |issue=14 |pages=3722–30 |date=July 2012 |pmid=22665903 |doi=10.1158/1078-0432.CCR-12-0411 |url=}}</ref><ref name="pmid22025146">{{cite journal |vauthors=Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ |title=Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial |journal=J. Clin. Oncol. |volume=30 |issue=2 |pages=134–41 |date=January 2012 |pmid=22025146 |pmc=3675689 |doi=10.1200/JCO.2011.35.5040 |url=}}</ref> | |||
* For [[patients]] with [[renal dysfunction]], the dose should be reduced to 200 mg daily. | |||
* Common [[side effects]] include: | |||
** [[Diarrhea]]/[[colitis]] | |||
** [[Rash]] | |||
** [[Dermatitis]] | |||
** [[Nausea]] | |||
** [[Hypertension]] | |||
** [[Headache]] | |||
** [[Fatigue]] | |||
** [[Anorexia]] | |||
** [[Abdominal pain]] | |||
** [[Hypocalcemia]] | |||
** [[Hypoglycemia]] and elevated [[alanine aminotransferase]] ([[ALT]]) | |||
* [[Patients]] require periodic assessment of the followings: | |||
**[[Electrocardiograms]] ([[ECG]]) | |||
** [[Serum potassium]] | |||
** [[Calcium]] | |||
** [[Magnesium ]] | |||
** [[TSH]] | |||
* Alternative regimen: [[Cabozantinib]] 140 mg PO daily until [[disease]] progression or unacceptable [[toxicity]].<ref name="pmid29045520">{{cite journal |vauthors=Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, Licitra L, Krajewska J, Kreissl MC, Niederle B, Cohen EEW, Wirth L, Ali H, Clary DO, Yaron Y, Mangeshkar M, Ball D, Nelkin B, Sherman S |title=Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma |journal=Ann. Oncol. |volume=28 |issue=11 |pages=2813–2819 |date=November 2017 |pmid=29045520 |pmc=5834040 |doi=10.1093/annonc/mdx479 |url=}}</ref><ref name="pmid25056653">{{cite journal |vauthors=Hoy SM |title=Cabozantinib: a review of its use in patients with medullary thyroid cancer |journal=Drugs |volume=74 |issue=12 |pages=1435–44 |date=August 2014 |pmid=25056653 |doi=10.1007/s40265-014-0265-x |url=}}</ref> | |||
* [[Patients]] should be monitored periodically for serum level of [[electrolytes]], [[calcium]], and [[TSH]]. | |||
===Radiation=== | ===Radiation=== | ||
[[External beam radiotherapy]] is recommended when there is a high risk of regional recurrence, even after optimum surgical treatment. | * [[External beam radiotherapy]] is recommended when there is a high risk of regional recurrence, even after optimum [[surgical]] treatment. | ||
* 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> | |||
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> | |||
===Hormone Therapy=== | ===Hormone Therapy=== | ||
* Hormonal therapy is given to replace the thyroid hormones normally made by the thyroid gland. TSH suppression, brought on by thyroid hormone replacement, does not reduce the | * [[Hormonal therapy]] is given to replace the thyroid hormones normally made by the [[thyroid gland]]. [[TSH|Thyroid stimulation hormone]] suppression, brought on by [[thyroid hormone]] replacement, does not reduce the risk of medullary thyroid cancer recurrence like it does in [[Papillary thyroid cancer|papillary]] and [[follicular thyroid cancer]]. | ||
==Reference== | ==Reference== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
[[Category:Endocrine system]] | |||
[[Category:Endocrinology]] | |||
[[Category:Otolaryngology]] | |||
[[Category:Disease]] | |||
[[Category:Genetic disorders]] | |||
[[Category:Types of cancer]] | |||
[[Category:Hereditary cancers]] | |||
Latest revision as of 13:57, 30 September 2019
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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
The predominant therapy for medullary thyroid cancer is surgical resection. Adjunctive chemo radiation may be required. The optimal therapy for medullary thyroid cancer depends on the stage at diagnosis.
Medical Therapy
Protein kinase inhibitors
- 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.[1]
- Cabozantinib, was granted marketing approval (November 2012) by the U.S. FDA for this indication.[2]
- Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial.
- Clinical trials of protein kinase inhibitors,[3] 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.
Adult
- Preferred regimen: Vandetanib 300 mg PO daily until disease progression or unacceptable toxicity.[4][5]
- For patients with renal dysfunction, the dose should be reduced to 200 mg daily.
- Common side effects include:
- Patients require periodic assessment of the followings:
- Alternative regimen: Cabozantinib 140 mg PO daily until disease progression or unacceptable toxicity.[6][7]
- Patients should be monitored periodically for serum level of electrolytes, calcium, and TSH.
Radiation
- External beam radiotherapy is recommended when there is a high risk of regional recurrence, even after optimum surgical treatment.
- Unlike other differentiated thyroid carcinoma, there is no role for radioiodine treatment in medullary-type disease.[8]
Hormone Therapy
- Hormonal therapy is given to replace the thyroid hormones normally made by the thyroid gland. Thyroid stimulation hormone suppression, brought on by thyroid hormone replacement, does not reduce the risk of medullary thyroid cancer recurrence like it does in papillary and follicular thyroid cancer.
Reference
- ↑ "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.
- ↑ "American Thyroid Association - Thyroid Clinical Trials". Retrieved 2007-12-21.
- ↑ Thornton K, Kim G, Maher VE, Chattopadhyay S, Tang S, Moon YJ, Song P, Marathe A, Balakrishnan S, Zhu H, Garnett C, Liu Q, Booth B, Gehrke B, Dorsam R, Verbois L, Ghosh D, Wilson W, Duan J, Sarker H, Miksinski SP, Skarupa L, Ibrahim A, Justice R, Murgo A, Pazdur R (July 2012). "Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary". Clin. Cancer Res. 18 (14): 3722–30. doi:10.1158/1078-0432.CCR-12-0411. PMID 22665903.
- ↑ Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ (January 2012). "Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial". J. Clin. Oncol. 30 (2): 134–41. doi:10.1200/JCO.2011.35.5040. PMC 3675689. PMID 22025146.
- ↑ Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, Licitra L, Krajewska J, Kreissl MC, Niederle B, Cohen E, Wirth L, Ali H, Clary DO, Yaron Y, Mangeshkar M, Ball D, Nelkin B, Sherman S (November 2017). "Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma". Ann. Oncol. 28 (11): 2813–2819. doi:10.1093/annonc/mdx479. PMC 5834040. PMID 29045520. Vancouver style error: initials (help)
- ↑ Hoy SM (August 2014). "Cabozantinib: a review of its use in patients with medullary thyroid cancer". Drugs. 74 (12): 1435–44. doi:10.1007/s40265-014-0265-x. PMID 25056653.
- ↑ 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.