A Phase II clinical trial with Pazopanib for the treatment of advanced differentiated thyroid cancer which stops tumor blood vessel growth had promising results. 49% of patients responded positively to Pazopanib therapy, their tumors shrank – the researchers estimate that at least two-thirds of them will probably have a response which lasts longer than one year, according to an article published in the medical journal The Lancet Oncology. This is the highest response rate for any treatment for advanced thyroid cancer ever, the investigators write.

The incidence of thyroid cancer has doubled over the last ten years. The majority of individuals with differentiated thyroid cancers have a favourable outcome with surgery and radioiodine.

About 1 in every 20 of these patients develop rapidly progressing disease with few treatment options.

“Differentiated” cancers are those in which the cells are mature and look like the cells in tissue where they came from.

According to recent research, drugs that target the growth of new blood vessels that help the tumor grow and spread – antiangiogenetic drugs – show promise for such patients.

Keith Bible from the Mayo Clinic, Rochester, USA, and team examined the safety and efficacy of pazopanib, which targets receptors on proteins involved in the process of developing new blood vessels (angiogenesis), including VEGF (vascular endothelial growth factor), platelet-derived growth factor, and c-Kit.

The researchers found that:

  • Of the 37 trial participants, all with rapidly progressing thyroid cancer, 18 of them (49%) had their tumors shrink.
  • A higher proportion of individuals with follicular thyroid cancer (73%) had their tumors shrink, compared to those with the more common papillary thyroid cancer (33%).
  • Although side-effects were common, they were mostly mild, including diarrhea, raised blood pressure (hypertension), and higher aminotransferase concentrations.

The doctors lowered the treatment dose for 15 patients because of side effects.

The researchers concluded:

The partial response rate for pazopanib in our study seems very favourable in the light of results from previous trials and, to our knowledge, represents the highest response rate yet reported in patients with differentiated thyroid cancers. Moreover, pazopanib seemed to modify the disease course in responders.

Martin Schlumberger, from the Institut Gustave Roussy, France, wrote in an accompanying Comment:

Additional trials are needed to compare the efficacy and toxic effects of kinase inhibitors, used alone or in combination with conventional treatments, and to determine the benefits in terms of progression-free and overall survival…Patients should preferably be included in such trials rather than be treated off-label with drugs that are available for other cancer types.

Thyroid cancer, or cancer of the thyroid is cancer of the thyroid gland, which is located in the front of the neck – the thyroid gland produces hormones which regulate normal body metabolism, heart rate, blood pressure, body temperature and weight. It is not a common type of cancer, although its incidence is rising.

There are various types of thyroid cancer:

  • Papillary thyroid cancer – accounts for about 80% of all cases. It is most commonly diagnosed in patients aged between 30 and 50 years of age.
  • Follicular thyroid cancer – accounts for about 11% of all cases. It is most commonly diagnosed in individuals aged 50 years or more.
  • Medullary thyroid cancer – accounts for about 4% of all cases. Some patients have a genetic fault (mutation) and commonly have cancer in other glands as well.
  • Anaplastic thyroid cancer – accounts for about 1% or 2% of all cases. It is most commonly diagnosed in patients over 60 years of age. It is an aggressive cancer.
  • Thyroid lymphoma – accounts for about 1% to 2% of all cases. This rare cancer typically affects patients aged over 70 years. It begins in the immune system cells in the thyroid gland.

Medullary, anaplastic and thyroid lymphoma are usually more aggressive and more likely to spread.

Thyroid cancer affects both men and women, but women are more likely to get it (75% of all cases).

According to the CDC (Centers for Disease Control and Prevention), USA, approximately 37,000 Americans are diagnosed with thyroid cancer annually. The National Health Service (NHS), UK, informs that thyroid cancer accounts for about 1% of all cancers diagnosed in the United Kingdom. In England and Wales (not including Scotland or Northern Ireland) approximately 1,200 new cases are diagnosed each year.

The following risk factors are linked to a higher probability of developing thyroid cancer:

  • Radiation exposure – especially in early childhood, increases the risk of developing thyroid cancer. This could be due to an all-nuclear fallout that occurs after a nuclear explosion, or radiation treatment for medical conditions/diseases when radiation risks were not properly understood (before the early 1960s).
  • Gender – three-quarters of all patients with thyroid cancer are female. This does not mean a woman will get thyroid cancer, which is a rare disease.
  • Some health conditions/diseases – people with the following conditions/diseases have a higher risk of developing thyroid cancer: Hashimoto’s thyroiditis, Cowden’s syndrome, thyroid adenoma and familial adenomatous polyposis.
  • Genetics – some inherited conditions increase the risk of developing medullary thyroid cancer. Approximately one quarter of individuals who develop medullary thyroid cancer have and abnormal gene.
  • Family history – individuals with a family history of goiter (thyroid gland enlargement) have a higher risk of developing thyroid cancer.

Click here to read about thyroid cancer in more detail.

Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic diff erentiated thyroid cancers: results of a phase 2 consortium study (PDF)
Keith C Bible, Vera J Suman, Julian R Molina, Robert C Smallridge, William J Maples, Michael E Menefee, Joseph Rubin, Kostandinos Sideras, John C Morris III, Bryan McIver, Jill K Burton, Kevin P Webster, Carolyn Bieber, Anne M Traynor, Patrick J Flynn, Boon Cher Goh, Hui Tang, Susan Percy Ivy, Charles Erlichman
The Lancet Oncology Published Online September 17, 2010
DOI:10.1016/S1470-2045(10)70203-5

Written by Christian Nordqvist