Use of Tyrosine Kinase Inhibitors for Treatment of Medullary Thyroid Carcinoma

Author(s):  
Ramona Dadu ◽  
Mimi N. Hu ◽  
Elizabeth G. Grubbs ◽  
Robert F. Gagel
2020 ◽  
Vol 52 (08) ◽  
pp. 588-597 ◽  
Author(s):  
Maran Ilanchezhian ◽  
Sophia Khan ◽  
Christian Okafor ◽  
John Glod ◽  
Jaydira Del Rivero

AbstractMedullary Thyroid Carcinoma (MTC) is a rare neuroendocrine cancer that accounts for 1–2% of thyroid cancers in the United States (U.S.). While most cases are sporadic, 25% of MTC cases are hereditary. These hereditary cases occur in the setting of Multiple Endocrine Neoplasia Type 2A (MEN2A) or 2B (MEN2B) driven by mutations in the Rearranged during Transfection RET proto-oncogene. This article discusses hereditary MTC in the setting of MEN2 and the treatment options available for it. The first line treatment for this disease is typically a total thyroidectomy and tyrosine kinase inhibitors. Two tyrosine kinase inhibitors, vandetanib and cabozantinib, have been approved for treatment of advanced MTC, but options beyond those are limited. However, several promising treatments are being studied, which are discussed in this review.


2013 ◽  
Vol 60 (3) ◽  
pp. 152-153
Author(s):  
Antonia García-Martín ◽  
Pablo José López-Ibarra Lozano ◽  
Eva María Triviño-Ibáñez ◽  
Fernando Escobar-Jiménez

Surgery ◽  
2004 ◽  
Vol 135 (2) ◽  
pp. 241-242 ◽  
Author(s):  
Ivan Plaza Menacho ◽  
Jan Willem de Groot ◽  
Thera Links ◽  
John Plukker ◽  
Bart J.L. Eggen ◽  
...  

2021 ◽  
Vol 53 (03) ◽  
pp. 149-160
Author(s):  
Frederik A. Verburg ◽  
Holger Amthauer ◽  
Ina Binse ◽  
Ingo Brink ◽  
Andreas Buck ◽  
...  

AbstractNotwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.


2016 ◽  
Vol 63 (7) ◽  
pp. 597-602 ◽  
Author(s):  
Yasuhiro Ito ◽  
Shinichi Suzuki ◽  
Ken-ichi Ito ◽  
Tsuneo Imai ◽  
Takahiro Okamoto ◽  
...  

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233720
Author(s):  
Viktor Sandblom ◽  
Johan Spetz ◽  
Emman Shubbar ◽  
Mikael Montelius ◽  
Ingun Ståhl ◽  
...  

2018 ◽  
Vol 127 (04) ◽  
pp. 240-246 ◽  
Author(s):  
Judit Kocsis ◽  
Éva Szekanecz ◽  
Ali Bassam ◽  
Andrea Uhlyarik ◽  
Zsuzsanna Pápai ◽  
...  

Abstract Background Medullary thyroid cancer (MTC) is a rare disease, the prognosis of advanced and metastatic disease is poor and few therapeutic options are available in this setting. Based on the results of phase II and III studies with sorafenib in differentiated thyroid cancer and the lack of availability of registered tyrosine kinase inhibitors, vandetabin and cabozantinib in Hungary, we designed a uncontrolled, prospective efficacy and safety study of patients with metastatic MTC treated with first-line sorafenib in five Hungarian oncology centers. Methods Ten consecutive patients with progressive or symptomatic metastatic MTC were included and started sorafenib 400  mg twice a day between June 2012 and March 2016. The primary end point was median progression-free survival (mPFS). Secondary endpoints included disease control rate, biochemical response, symptomatic response and toxicity. Results Four patients achieved partial remission (40%) according to RECIST 1.1 evaluation. Five patients had stable disease beyond 12 months (50%) and one patient had progressive disease (10%). Median PFS was 19.1 months. The disease control rate was 90%. Association between radiologic response and biochemical or symptomatic response was inconsistent. Most common side effects were Grade 1-2 fatigue (60%), palmar-plantar erythrodysesthesia, rash/dermatitis 50-50%, alopecia 40%. Conclusions In our prospective case series in patients with MTC first-line sorafenib showed at least similar efficacy as in other small phase II trials and case reports. Based on comparable efficacy with registered tyrosine kinase inhibitors and it’s manageable toxicity profile, we believe that sorafenib has role in the sequential treatment of MTC.


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