Rapid Response to Sorafenib in Metastatic Medullary Thyroid Carcinoma

Frank‐Raue, Karin; Ganten, Maria-Katharina; Kreißl, Michael C.; Raue, Friedhelm

doi:10.1055/s-0030-1262836

Cited by 17 publications

(14 citation statements)

References 10 publications

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“…In an off-label observational study, five patients with progressive metastatic MTC were treated with sorafenib (400 mg twice daily). Two patients showed a partial response and two patients experienced stable disease (Frank-Raue et al 2011). In a recently published retrospective longitudinal study of 12 patients with progressive metastatic MTC, 10 patients showed stable disease (83.3%), no PR was observed.…”

Section: Sorafenibmentioning

confidence: 87%

New drugs for medullary thyroid cancer: new promises?

Spitzweg¹,

Morris²,

Bible³

2016

Endocrine-Related Cancer

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Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives.

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Section: Sorafenibmentioning

confidence: 87%

New drugs for medullary thyroid cancer: new promises?

Spitzweg¹,

Morris²,

Bible³

2016

Endocrine-Related Cancer

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“…The treatment was prematurely terminated in MTC hereditary patients due to slow accrual [85]. In a similar trial, all 5 patients treated with sorafenib exhibited partial responses [86]. Recently, a study of sorafenib was conducted on advanced thyroid carcinoma patients, and partial responses were reported in six out of the 12 (50%) patients with MTC, although the small number of patients requires further prospective studies [87].…”

Section: Potential Targeted Therapies For Mtcmentioning

confidence: 99%

Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

Giunti

Antonelli

Amorosi

et al. 2013

International Journal of Endocrinology

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Parafollicular C-cell-derived medullary thyroid cancer (MTC) comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET) and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR) cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

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“…A small observational study investigated the efficacy of sorafenib in five patients with progressive MTC; after 6 months, two patients showed a partial response, and two patients exhibited SD 77. In a phase II trial, 21 patients with metastatic or locally advanced MTC, hereditary or sporadic form, were enrolled to receive 400 mg sorafenib orally twice daily.…”

Section: Review Of Therapies Targeting Receptor Tyrosine Kinasesmentioning

confidence: 99%

Advanced medullary thyroid cancer: pathophysiology and management

Ferreira¹,

Siqueira²,

Ceolin³

et al. 2013

CMAR

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Medullary thyroid carcinoma (MTC) is a rare malignant tumor originating from thyroid parafollicular C cells. This tumor accounts for 3%–4% of thyroid gland neoplasias. MTC may occur sporadically or be inherited. Hereditary MTC appears as part of the multiple endocrine neoplasia syndrome type 2A or 2B, or familial medullary thyroid cancer. Germ-line mutations of the RET proto-oncogene cause hereditary forms of cancer, whereas somatic mutations can be present in sporadic forms of the disease. The RET gene encodes a receptor tyrosine kinase involved in the activation of intracellular signaling pathways leading to proliferation, growth, differentiation, migration, and survival. Nowadays, early diagnosis of MTC followed by total thyroidectomy offers the only possibility of cure. Based on the knowledge of the pathogenic mechanisms of MTC, new drugs have been developed in an attempt to control metastatic disease. Of these, small-molecule tyrosine kinase inhibitors represent one of the most promising agents for MTC treatment, and clinical trials have shown encouraging results. Hopefully, the cumulative knowledge about the targets of action of these drugs and about the tyrosine kinase inhibitor-associated side effects will help in choosing the best therapeutic approach to enhance their benefits.

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Rapid Response to Sorafenib in Metastatic Medullary Thyroid Carcinoma

Abstract: These data suggest a possible role for sorafenib in the treatment of progressive metastatic MTC.

Cited by 17 publications

References 10 publications

New drugs for medullary thyroid cancer: new promises?

New drugs for medullary thyroid cancer: new promises?

Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

Advanced medullary thyroid cancer: pathophysiology and management

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