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Motesanib Diphosphate Provides Anticancer Activity Among Patients with Progressive Thyroid Cancer


The investigative agent motesanib diphosphate (AMG 706) produces a regression of cancer among patients with thyroid cancer that is progressing despite standard therapies. These results were recently published in the New England Journal of Medicine.
The thyroid is a gland in the throat that produces hormones mostly related to metabolic processes in the body. According to the American Cancer Society, approximately 37,340 new cases of thyroid cancer will be diagnosed in 2008 in the United States. Nearly two-thirds of all thyroid cancers occur in people between the ages of 20 and 55. Overall, thyroid cancer is considered to be a highly curable cancer, with 97% of individuals alive at least five years following diagnosis. Nearly 95% of all thyroid cancers are classified as differentiated thyroid cancers, which refers to the type and characteristics of the cancer cells.
Standard therapy for thyroid cancer includes the removal of the thyroid, which is followed by drugs to suppress certain hormone levels related to the thyroid and radiation plus iodine (radioiodine) therapy, which is targeted to eliminate any remaining thyroid cancer cells. Patients whose thyroid cancer progresses or fails following standard therapy have a 10-year survival rate of less than 15%. Thus, novel agents targeting progressive thyroid cancers are needed.
The vascular endothelial growth factor (VEGF) is a protein that is an important component to cellular growth and replication. Often, cancer cells will have an overexpression or mutation of VEGF. Targeted therapies, including those targeted against VEGF, have recently demonstrated anticancer activity in certain types of cancers. Research into blocking VEGF continues in clinical trials.
Researchers from the M.D. Anderson Cancer Center recently conducted a clinical trial to evaluate motesanib diphosphate, a VEGF inhibitor, for the treatment of differentiated thyroid cancers that progress following standard therapies. This trial included 93 patients whose cancer had progressed following standard radioiodine therapy.
Anticancer responses were achieved in 14% of patients.
Disease stabilization was achieved in 67% of patients.
35% of patients achieved disease stabilization for at least six months.
The median duration of anticancer responses was 32 weeks.
Median progression-free survival was 40 weeks.
The most common side effects of therapy were diarrhea, increased blood pressure, fatigue, and weight loss.
The researchers concluded that motesanib diphosphate appears to provide significant anticancer activity, as well as long-lasting disease stabilization, in advanced thyroid cancer that progresses following standard therapies. Patients with progressive thyroid cancers may wish to speak with their physician regarding their individual risks and benefits of participating in a clinical trial further evaluating therapies such as motesanib diphosphate or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and
www.eCancerTrials.com.
Reference: Sherman S, Wirth L, Droz J-P, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. New England Journal of Medicine.

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