Thyroid, Kidney Cancers May Share Treatment

Thyroid Cancer and Kidney Cancer May Share Same Treatment

The thyroid gland is located at the base of the neck just below the Adam's apple and produces hormones that regulate your heart rate, blood pressure, body temperature and weight.  Thyroid cancer occurs in the cells of the thyroid.

According to the National cancer Institute (NCI) approximately 37,000 Americans are diagnosed with cancer each year, however thyroid cancer rates are increasing; possibly as a result of new technology allowing doctors to find small thyroid cancers that may not have been found previously.

In Phase II study led by Keith bible, MD, Mayo Clinic, Rochester, MN of GlaxoSmithKline's cancer drug Votrient, results indicated the kidney drug helped shrink tumors in nearly half of patients with an advanced form of thyroid cancer, as reported in The Lancet Oncology Friday.

About 49% of the participants in the trial with radioiodine-refractory progressive differentiated thyroid cancer showed a partial response with the use of pazopanib (Votrient), with a 66% likelihood that it would be sustained for at least a year,  according to the report.  Adverse side-effects were common, and whether there would be a survival benefit from pazopanib remain unclear.

Researchers wrote, "given the promising activity of pazopanib noted in this trial, we are currently undertaking further investigations including an expanded cohort of patients with differentiated thyroid cancers, as well as separate cohorts of patients with medullary or anaplastic thyroid cancers."

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

Direct trials between differentiated thyroid cancers isn't possible, but researchers remain optimistic as the response rate with a tyrosine-kinase inhibitor was the highest currently reported.

Martin Schlumberger, MD, of the Institut Gustave Roussy in Villejuif, France, said in an accompanying editorial, "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 benefits in terms of progression-free and overall survival.  They would have to be multicenter trials, because patients with refractory and progressive disease are rare."

While most patients with differentiated thyroid cancers have good results with surgery, suppression of thyroid-stimulating hormone secretion with levothyroxine, therapeutic radioiodine and radiation therapy, progression of the disease is seen in about 5% of patients with advanced disease and typically chemotherapy is not effective.  Tyrosine kinase inhibitors have been researched in these patients because kinases are activated in the disease.  Kinases is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP[2], to specific substrates

Participants received 800mg of continuous pazoparib, an approved treatment of renal cell carcinoma, in four week cycles until disease progression, drug intolerance or both occurred.  The median number of cycles completed was 12; 43% of patients required a dose reduction due to common side effects.

Two patients discontinued treatment because of serious hemorrhagic events and fully recovered. Another two patients died -- one from a massive MI and the other from complications of surgery to treat acute cholecystitis.

"Although in both cases the patients had preexisting disorders, we cannot exclude some contribution of pazopanib," Bible and his colleagues wrote.

Most commonly reported minor side effects were fatigue, skin and hair hypopigmentation (discoloration), diarrhea and nausea; many patients revealed hypertension which was easily managed; there were no cases of heart failure or arrhythmic events.

None of the patients had a complete response to the drug, but the 49% who had partial response far exceeded the 20% threshold needed to label the treatment "promising" by researchers.

Past history indicated a favorables resuts with pazopanib as previous trials revealed 73% of patients with follicular tumors, 45% of patients with Hurthle cell tumors and 33% of patients with papillary tumors had positive responses.  Researchers noted that the differences need to be confirmed.

If confirmed, "they raise the critical question as to whether identifiable genetic or other differences between thyroid cancer histological subtypes can affect responsiveness to pazopanib and potentially to other tyrosine kinase inhibitors," they wrote.

Consistent suppression of thyroid-stimulating hormone did not seem to affect tumor response.  There was no relationship between treatment response and plasma concentrations of several biomarkers, including interleukins 6 and 8, hepatocyte growth factor, E-selectin, VEGF, and platelet-derived growth factor.

At one year, median survival was 81% and progression-free survival was 47%.  At the latest follow-up, 12 patients were alive without disease progression, 15 were alive with progressive disease, and 10 had died.