Drug May Slow Some Thyroid Cancers
CancerWise - October 2008
Thyroid cancer that metastasizes (spreads to other parts of the body) usually has a poor outcome, but an experimental drug that stops tumors from forming blood vessels slowed the growth of the disease in more than half of the patients in a recent study.
Researchers at M. D. Anderson led the international study team representing 42 institutions in 10 countries. Findings were published in the July 3 edition of the New England Journal of Medicine.
This study looked at the drug motesanib diphosphate (AMG 706), which targets a protein known as vascular endothelial growth factor (VEGF). VEGF helps form new blood vessels, which allows tumors to grow and spread. VEGF plays a key part in the spread of thyroid cancer.
Significance of results
The experimental treatment represents a possible new therapy for patients with advanced disease, says the study’s lead author Steven Sherman, M.D., chair and professor in M. D. Anderson’s Department of Endocrine Neoplasia and Hormonal Disorders.
“There’s basically no treatment for advanced metastatic thyroid cancer,” Sherman says. “Most patients are not treated with chemotherapy because the response rate is usually less than 25%. The limited benefits rarely justify the side effects.”
Earlier stage thyroid cancers can be treated successfully by surgical removal of the thyroid. Surgery usually is followed by treatment with radioactive iodine and lifelong thyroid hormone replacement therapy.
But in about 15% of patients the cancer spreads, usually to the lungs. A few of these patients respond to radioactive iodine, but most survive only two to four years.
A Phase I trial at MD Anderson identified the potential benefit of AMG 706 in advanced thyroid cancer. Two of five study patients with metastasized thyroid cancer responded to the drug, which resulted in Sherman’s Phase II study of the drug.
The Phase II study enrolled 93 patients with advanced thyroid cancer that had not responded to radioactive iodine treatment.
Participants took 125 milligrams of AMG 706 once a day for 48 weeks or until they experienced unacceptable side effects or became too ill to continue treatment.
Tumors were examined with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the neck, chest and abdomen every eight weeks or if the cancer seemed to be getting worse.
If the tumor showed a response, the scans were repeated four or more weeks later.
Of the 93 trial participants, 49 had positive responses.
Of the 49 patient tumors:
- 14% reduced in size
- 35% stopped growing for more than six months
Thirty-two patients completed the full 48 weeks of treatment.
Of those patients who discontinued treatment:
- 35 stopped because the disease progressed
- 12 stopped because of side effects
- Five died from advanced disease
- Nine stopped for non-health related reasons
- 87 patients (94%) experienced at least one treatment-related side effect
In half of these patients, the side effects were classified as severe: five patents had life-threatening side effects.
An analysis of 25 patients showed that tumors with a genetic mutation known as BRAF V600E responded best to AMG 706.
Additional research is needed on the connection between BRAF V600E and AMG 706.
“This is the first study to find that a specific gene mutation might cause thyroid cancer to be more likely to respond to a drug,” Sherman says. “This might allow us to individualize therapy and have a higher level of success in the future.”
— Adapted by Dawn Dorsey from an M. D. Anderson news release
MD Anderson resources:
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