Phase II Trial of REVLIMID® (Lenalidomide) for Therapy of Radioiodine-Unresponsive Papillary & Follicular Thyroid Carcinomas
Thalidomide has found new uses as a tumor anti-angiogenesis agent that is capable of
diminishing the proliferation of angiogenesis-dependent solid malignancies. Distantly
metastatic, unresectable medullary thyroid carcinomas, as well as de-differentiated
papillary and follicular thyroid carcinomas, which no longer concentrate radioiodine, have
no known effective systemic therapies. We have verified, in the context of a completed phase
2 clinical trial, that thalidomide has significant activity in thyroid carcinomas that are
no longer radioiodine avid and are rapidly progressive. This activity has only limited
durability of around 7 months and is associated with significant toxicities of sedation,
constipation and neuropathy.
REVLIMID® (lenalidomide) is an analog of thalidomide with the chemical name,
alpha-(3-aminophthalimido) glutarimide. REVLIMID® is noted to be more potent than
thalidomide in inhibiting the production of TNF-alpha. It has more than doubled the
inhibition of microvessel growth at the same concentration as thalidomide in a rat aorta
angiogenesis model as well as greatly enhanced activity as an IMiD. Most importantly, it
lacks much of the toxicity of thalidomide, particularly in regards to somnolence,
neuropathy, or biochemical effects. In fact, patients with multiple myeloma, known to be
resistant to thalidomide, were still seen to exhibit clinical responses to REVLIMID®. This
makes REVLIMID® an appropriate agent to investigate in a phase 2 trial in thyroid carcinoma.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Kenneth B Ain, M.D.
University of Kentucky
United States: Food and Drug Administration
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