PD1-4 - Molecular Targeting Therapy for Thyroid Cancer: Problems in Clinical Practice

Abstract

Several molecular targeting drugs, especially RAF-, RET- and/or VEGFR-targeting drugs have been developed for thyroid cancer. Sorafenib for differentiated cancer and vandetanib for medullary cancer are approved in US and will be approved in Japan in near future. Those drugs have some unique adverse events (AEs) and should be properly managed for effective therapy.Sorafenib is a multi-tyrosine kinase inhibitor (TKI) and inhibits RAF, VEGFR-2,3, PDGFR, c-kit, Flt-3, and already approved for renal cell carcinoma and hepatic cell carcinoma in Japan. Major AEs caused by sorafenib are hypertension, hand foot syndrome (HFS), eruption, diarrhea, and fatigue, and considered to be mainly caused by VEGFR inhibition.Hypertension usually develops early (within 6 weeks), and mostly controlled by antihypertensive drugs such as Ca antagonists or angiotensin receptor blockers. HFS can have a significant impact on QOL of patients, and seems more frequent in thyroid cancer patients and Japanese. It often develops early (within 1-2 weeks) at regions with mechanical stress. Preventive measures such as keeping skin clean, removal of hyperkeratotic areas, and usage of cushioning are recommended. If symptoms reach grade 2 or more, the mainstay of management is dose modification, but supportive treatment, topical corticosteroid and analgesics should be used. Eruptions are usually mild, but Japanese patients occasionally cause erythema multiforme or Stevens-Johnson syndrome. Diarrhea is frequent especially in patients treated for long time, but severe cases are rare. Severe fatigue is also infrequent.Endocrine surgeons who mainly treat thyroid cancer are not familiar with AEs of TKIs, so cooperation with medical oncologist and team-oriented therapy with nurses, pharmacists, or others are very important for effective therapy with molecular targeting agents.