A Phase II Study of Imatinib in Patients with Advanced Anaplastic Thyroid Cancer

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 signalling 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 randomised 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 summarise the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.

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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

US Endocrinology ◽

10.17925/use.2012.08.02.122 ◽

2012 ◽

Vol 08 (02) ◽

pp. 122

Author(s):

Jochen Lorch ◽

Wieland Voigt ◽

◽

Keyword(s):

Thyroid Cancer ◽

Phase Ii ◽

Kinase Inhibitor ◽

Treatment Strategies ◽

Anaplastic Thyroid Cancer ◽

Phase Iii ◽

Clinical Activity ◽

Phase Ii Trials ◽

New Era ◽

Cancer Subtypes

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.

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A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.5502 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 5502-5502 ◽

Cited By ~ 19

Author(s):

J. A. Sosa ◽

R. Elisei ◽

B. Jarzab ◽

C. S. Bal ◽

H. Koussis ◽

...

Keyword(s):

Survival Analysis ◽

Thyroid Cancer ◽

Phase Ii ◽

Anaplastic Thyroid Cancer ◽

Vascular Disrupting Agent ◽

Randomized Phase Ii ◽

Final Survival ◽

Vascular Disrupting

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A phase II study of a yeast-based therapeutic cancer vaccine, GI-6207, targeting CEA in patients with minimally symptomatic, metastatic medullary thyroid cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps3127 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS3127-TPS3127

Author(s):

Ravi Amrit Madan ◽

Nishith K. Singh ◽

Ann Wild Gramza ◽

Antonio Tito Fojo ◽

Christopher Ryan Heery ◽

...

Keyword(s):

Thyroid Cancer ◽

Tumor Growth ◽

Phase Ii ◽

Cancer Vaccine ◽

Growth Rates ◽

Medullary Thyroid Cancer ◽

Phase Ii Study ◽

Therapeutic Cancer Vaccine ◽

Long Term Outcome ◽

Medullary Thyroid

TPS3127 Background: Saccharomyces cerevisiae has been genetically modified to express CEA protein and developed under a CRADA with GlobeImmune/NCI as a heat-killed immune-stimulating, therapeutic cancer vaccine (GI-6207). A phase I study with GI-6207 demonstrated safety, biomarker stabilization and enhanced immune response in some patients. CEA is over-expressed in multiple malignancies, including medullary thyroid cancer (MTC). Two therapies recently approved by the FDA for metastatic MTC (vandetanib, cabozantinib) come with toxicity and should be reserved for symptomatic/progressive disease. However, a large population of asymptomatic MTC patients has small tumor burden and/or disease that is more indolent. The standard management of these patients is observation. Preliminary data suggest that tumor growth measured by the rate of CEA and calcitonin increase can be quantified in a 3-6 months. Retrospective data from prostate cancer studies suggest vaccines can alter growth rates within 3-4 months. We hypothesize that GI-6207 can alter tumor growth rates in MTC and impact long-term outcome. Methods: A phase II study will evaluate the effect of GI-6207 onthe rates ofincrease in calcitonin in metastatic MTC. 34 patients with minimally symptomatic, radiographically evaluable, metastatic MTC will be randomized 1:1. Arm A will receive vaccine for a year from the time of enrollment. Arm B will receive vaccine after 6 months of surveillance. GI-6207 will be administered subcutaneously at 4 sites (10 yeast units/site), every 2 weeks for 3 months, then monthly up to 1 year. The primary endpoint will compare the effect of GI-6207 on calcitonin kinetics between the vaccine and surveillance arms in the first 6 months. Secondary endpoints include immunologic responses (including antigen-specific T cell responses), objective responses, time to progression, and changes in CEA kinetics. If this trial can prospectively demonstrate that vaccines can alter tumor growth rates, and if such changes are associated with clinical outcomes, then changes in tumor growth rates may become a clinical metric to evaluate vaccine efficacy in MTC and other populations.

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