Japanese clinical guidelines for molecular targeted therapies in the treatment of thyroid cancer

Abstract

Several oral multi-targeted kinase inhibitors (MKIs) have now been approved in Japan and other countries for advanced thyroid cancer, based on the results of phase III trials. In Japan, sorafenib and lenvatinib have been approved for unresectable differentiated as well as medullary and anaplastic thyroid cancer, and vandetanib has been approved for unresectable medullary thyroid carcinoma. However, optimal drug selection and timing of treatment remain controversial. In response, we have revised the Japanese clinical guidelines for thyroid tumors to recommend which, when and how these MKIs should be used for unresectable thyroid cancer. The goal of recurrent or metastatic cancer patients is extended survival while ensuring a good quality of life (QOL). The higher tumor shrinkage caused by MKIs relieves symptoms, and the longer disease control is associated with better QOL. Better tolerability can also avoid a deterioration in QOL. In other words, the first choice of treatment for these populations is the drug that demonstrates a higher response rate, longer PFS and best tolerability. The appropriate timing for the start of MKI is controversial, because the tumor growth of thyroid cancer is slower than that of other cancers, even if the tumor becomes radioiodine-refractory. Any consideration of their indications requires careful weighing of their relative merits and demerits. However, the decision of whether to hasten or delay the use of MKI in individual patients is not so simple. Furthermore, a watch and wait approach increases the risk of bleeding. Appropriate supportive care is also essential to avoid a deterioration in patient QOL. Further, improved infrastructure in the outpatient clinic and patient education are also essential in promoting early contact with medical providers.