Protein kinase inhibitor therapy in advanced thyroid cancer: ethical challenges and potential solutions

Protein kinase inhibitors (PKIs) have emerged as highly promising therapies in progressive metastatic radioiodine-refractory differentiated thyroid cancer and in medullary thyroid cancer; two were recently approved in the USA for use in medullary thyroid cancer (vandetanib, cabozantinib), and another for use in progressive metastatic radioiodine-refractory differentiated thyroid cancer (sorafenib). Although more than 90% of thyroid cancer patients fare well in response to conventional treatment, PKI therapy has the potential to provide benefit. Nonetheless, PKIs produce numerous side effects, may worsen quality of life, may hasten mortality (by 1-2%), require discerning clinical acumen, are not yet proven to improve thyroid cancer survival and are very costly. This raises questions about who should prescribe PKIs, and about whether their use in thyroid cancer is truly beneficent and ethically justified. Restraint should be exercised in their use in thyroid cancer, with potential risks and benefits carefully weighed and solutions devised to help ameliorate many of the problems associated with their use.