Lessons learned and questions unanswered from use of multitargeted kinase inhibitors in medullary thyroid cancer

摘要

Objectives To review studies of novel multitargeted kinase inhibitors studied in patients with medullary thyroid cancer (MTC). Materials and methods Search of relevant references in PubMed and Google Scholar on "chemotherapy" and "medullary thyroid cancer". Results Multitargeted kinase inhibitors have revolutionized the role of chemotherapy for progressive MTC, providing for the first time tolerable therapeutic options that can improve outcomes in patients with progressive disease. Drugs thought to inhibit the RET kinase have advanced the furthest for this disease, but these agents also target the VEGF receptor along with other kinases that may be relevant to both beneficial and adverse effects. Vandetanib improved progression-free survival from 19.3 to 30.5 months compared with placebo in patients with metastatic disease, whereas cabozantinib improved progression-free survival from 4.0 months to 11.2 months in a population with more aggressive disease. However, "cure" remains elusive, adverse events frequent, and exactly how such "targeted" agents actually function within MTC remains unclear. Conclusions New approaches to clinical trial design and the preclinical development of targeted agents may be required to optimize the combination of maximum efficacy with minimal toxicity for patients with metastatic MTC.