NEW YORK (Reuters Health) – The tyrosine-kinase inhibitor pazopanib seems to be a promising option for treating progressive metastatic differentiated thyroid cancer that is unresponsive to radioiodine therapy, an international group reports in The Lancet Oncology published online September 17.
Dr. Keith Bible with the Mayo Clinic in Rochester, Minnesota and colleagues note that most patients with differentiated thyroid cancer do well with traditional therapy, but about 5% develop progressive disease for which there are few therapeutic options.
“The realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors” the team explains. “We investigated the safety and efficacy of pazopanib.”
The phase II trial involved 37 patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers who were started on 800 mg pazopanib daily, administered continuously in 4-week cycles, until disease progression, drug intolerance, or both occurred.
Eighteen patients had a partial response, for a response rate of 49%, and the likelihood of a durable response (at least 1 year) was calculated to be 66%.
“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,” Dr. Bible and colleagues write.
Sixteen (43%) patients required dose reductions owing to adverse events such as fatigue, skin and hair hypopigmentation, diarrhea, and nausea.
In a commentary, Dr. Martin Schlumberger from the Institut Gustave Roussy in Villejuif, France points out that several kinase inhibitors have been successfully tested in phase II trials — motesanib, axitinib, sunitinib, and sorafenib.
“Additional trials are needed to compare the efficacy and toxic effects of kinase inhibitors, used alone or in combination with conventional treatments,” he recommends, “and to determine benefits in terms of progression-free and overall survival.”
Reference:
Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial
Lancet Oncol 2010.
