Advanced Thyroid Cancer Investigational Drug Shows Promise

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Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials;  Endocrinology
Article Date: 03 Jul 2008 - 12:00 PDT

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A study by an international team of researchers found that an experimental drug that stops blood vessels that feed tumors from forming was able, in a small number of patients, to slow down the progression of advanced thyroid cancer that has spread to other sites.

The study was the work of researchers from The University of Texas MD Anderson Cancer Center, and colleagues in 10 other countries, and is published in today's online issue of the New England Journal of Medicine.

There are few treatment options for patients who have advanced metastatic thyroid cancer (where it has started to spread to other parts of the body) and the prognosis is generally poor. However, thyroid cancer is supported by a protein called VEGF (vascular endothelial growth factor) which helps blood vessels that feed the cancer tumour to grow, so the researchers were keen to find out if a new drug that blocks VEGF might help to slow tumors in thyroid cancer.

Lead author Dr Steven I Sherman, chair and professor of MD Anderson's Department of Endocrine Neoplasia and Hormonal Disorders, explained the need to find effective treatments for advanced thyroid cancer:

"There is no standard accepted chemotherapy for advanced metastatic differentiated thyroid cancer, and response rates have typically been 25 per cent or less."

"Most patients are not treated with systemic chemotherapy because the limited benefit rarely justifies the side effects. Treatment of thyroid cancer has been a completely unmet need," he added.

So Sherman and colleagues decided to investigate whether a new VEGF inhibitor called motesanib diphosphate (AMG 706) might be effective.

They treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with a daily oral dose of 125 mg of motesanib diphosphate and arranged for independent radiographic monitoring of tumor progression.

The patients took the drug for 48 weeks, or until the side effects became unacceptable or the disease progressed.

The researchers measured the duration of the response, progression-free survival, drug safety and changes in blood levels of the tumor marker, thyroglobulin.

The results showed that:

• 49 per cent of the 93 patients had a positive response.


• 14 per cent of that group experienced tumor shrinkage.


• 67 per cent of the patients achieved a stable disease state.


• The stable state was maintained for 24 weeks or more in 35 per cent of the patients.


• 8 per cent of the patients had progressive disease as the best response.


• Median progression-free survival was estimated to be 40 weeks.


• Of 75 patients who had their blood thyroglobulin levels analysed, 81 per cent had lower levels during treatment than at baseline.


• 25 of the patients underwent genetic analysis that showed those who had a specific mutation known as BRAF V600E in their tumors had a better response to the experimental drug than those without it.


• The most common treatment-related adverse events were diarrhea (in 59 per cent of patients), hypertension (56 per cent), fatigue (46 per cent), and weight loss (40 per cent).

The authors concluded that:

"Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive."

Sherman said more research was need on the genetic findings, but these early results were a good start.

"Finding that patients whose tumors bear a particular mutation were more likely to respond to the drug is an example of where we would like to head in our research," said Sherman.

"This is the first of the various thyroid cancer trials to identify specific mutations that might allow us to individualize or personalize therapy," he added.

Most patients with papillary or follicular thyroid carcinomas will not die of their condition. These can be removed with surgery and usually respond well to radioactive iodine and lifelong thyroid hormone therapy.

But for 15 per cent of patients, the tumors become metastatic, and the cancer usually spreads to the lungs. A small proportion of those patients respond to radioactive iodine treatment and survive for many years, but others have a much poorer prognosis; fewer than 15 per cent live more than 10 years.

"Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer."
Sherman, Steven I., Wirth, Lori J., Droz, Jean-Pierre, Hofmann, Michael, Bastholt, Lars, Martins, Renato G., Licitra, Lisa, Eschenberg, Michael J., Sun, Yu-Nien, Juan, Todd, Stepan, Daniel E., Schlumberger, Martin J., the Motesanib Thyroid Cancer Study Group.
N Engl J Med 2008 359: 31-42.
Volume 359:31-42, July 3, 2008, Number 1

Click here for Abstract.

Source: Journal abstract, NEJM press release.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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