Targeted Therapy for Medullary Thyroid Cancer: A Review

Abstract

Medullary thyroid cancers (MTCs) constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS. The management of residual, recurrent, or metastatic disease till a few years ago was re-surgery with local measures such as radiation. Chemotherapy was used with marginal benefit. The development of targeted therapy has brought in a major advantage in management of such patients. Two drugs—vandetanib and cabozantinib—have been approved for use in progressive or metastatic MTC. In addition, several drugs acting on other steps of the molecular pathway are being investigated with promising results. Targeted radionuclide therapy also provides an effective treatment option with good quality of life. This review covers the rationale of targeted therapy for MTC, present treatment options, drugs and methods under investigation, as well as an outline of the adverse effects and their management.

Clinical utility of 177Lu‐DOTATATE PRRT in somatostatin receptor‐positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity

“…Multiple studies have demonstrated the important role of peptide receptor radionuclide therapy (PRRT) as a viable therapeutic option in somatostatin receptor expressing metastatic/advanced malignancies of neuroendocrine origin, with its possible beneficial effect on quality of life (QOL). 17 A fraction of MTC expresses high uptake on SSTR based imaging, making PRRT a potential and viable therapeutic option in these patients.…”

Role of tissue and circulating microRNAs and DNA as biomarkers in medullary thyroid cancer

“…In case of progression or recurrence, currently available treatments include the use of multi-tyrosine kinase inhibitors (TKI), which are not specific for RET inhibition (Filetti, et al, 2019). The two approved multi-TKI are vandetanib that targets RET, VEGFR, and cKIT, and cabozantinib, which targets RET, VEGFR, and EGFR (Kurzrock, et al, 2013;Priya, Dravid, Digumarti, & Dandekar, 2017). Both drugs are effective in delaying disease progression, but may not prolong survival and are associated with severe side effects for their wide spectrum of action .…”

Pazopanib, Cabozantinib, and Vandetanib in the Treatment of Progressive Medullary Thyroid Cancer with a Special Focus on the Adverse Effects on Hypertension

“…Tyrosine kinase inhibitors (TKIs), such as pazopanib and cabozantinib, are proposed as a promising new therapeutic option. TKIs work by blocking internal signaling cascades involved in the induction of angiogenesis, an important process for the tumor to acquire enough nutrients for further expansion [ 1 , 2 ]. However, such therapies also have adverse effects (AEs), and for tyrosine kinase inhibitors, two of the most common side effects are proteinuria and hypertension [ 3 ].…”