Progress in the treatment of advanced
medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years,
vandetanib and
cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple
kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including
hypertension,
hemorrhage/perforation,
diarrhea and other gastrointestinal events, several dermatologic events, and
hypothyroidism. In addition,
vandetanib is uniquely associated with QTc prolongation through interaction with myocardial
potassium channels, and
cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with
vandetanib and
cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and
dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with
vandetanib and
cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line
therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as
vandetanib and
cabozantinib, we commend that patients with advanced MTC be managed and treated by a
thyroid cancer specialist with coordination of care within a multidisciplinary team.