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Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer

Published Online: September 14th 2012 US Endocrinology, 2012;8(2):122-128 DOI: http://doi.org/10.17925/USE.2012.08.02.122
Authors: Jochen Lorch, Wieland Voigt
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Abstract:
Overview

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

Keywords

Anaplastic thyroid cancer, medullary thyroid cancer, targeted drugs, multimodality treatment

Article:

Malignancies of the thyroid can be classified as either of follicular cell origin or parafollicular C-cell origin.

Malignancies of the thyroid can be classified as either of follicular cell origin or parafollicular C-cell origin. The cancers of follicular origin include papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and Hurthle cell cancer commonly referred together as differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC).1 Medullary thyroid cancer (MTC) originates from the parafollicular C-cells.1 PTC and FTC account for more than 80–90 % of all thyroid cancers, MTC for about 4 %, PDTC for about 5–10 %, and ATC for 2–5 %.1,2 Although ATC represents only a minority of all thyroid cancer cases, it accounts for approximately 50 % of all thyroid cancer-related death.3 Its highly aggressive nature is underscored by a median survival rate of less than six months following diagnosis.3,4 While ATC has an almost uniformly fatal outcome despite aggressive therapy,1 unselected patients suffering from MTC have an overall 10-year survival of approximately 70 % following primary successful surgery5 (see Figure 1). However, until recently, only limited therapeutic options existed for patients with unresectable or metastatic MTC.6

Unlike in more frequent types of cancer, prospective randomized trials are difficult due to the lack of sufficient number of patients. Thus advances in the clinical care of ATC and MTC has been slow and mainly depend on retrospective data analysis or limited case series or even clinical case reports.

Surgery is considered the only curative treatment option in MTC.6 This contrasts with ATC, where the potential and optimal sequence of surgery, radiation, and chemotherapy still needs to be defined.7,8

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Article Information:
Correspondence

Wieland Voigt, MD, Associate Professor, Department of Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle/Saale, Germany. E: wieland.voigt@medizin.uni-halle.de

Received

2012-04-11T00:00:00

References

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