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Combinations and novel treatment approaches are currently under investigation as treatments for patients with medullary thyroid cancer (MTC). A phase II trial examined the combination of the mTOR inhibitor everolimus and the multikinase inhibitor sorafenib, explains Eric J. Sherman, MD. Sorafenib has a slight affect on RET and works synergistically with mTOR inhibition. Response rates to sorafenib alone are generally around 9%; however, the combination of everolimus and sorafenib more than quadruples responses to 44%, Eric Sherman explains.
In addition to this combination, the multitargeted kinase inhibitor lenvatinib is being explored in MTC, explains Eric Sherman. This agent inhibits VEGFR1-3, FGFR1-4, RET, KIT, and PDGFR-beta. In a phase II study, treatment with lenvatinib resulted in a response rate of 36%.
In addition to TKIs, researchers are examining chemotherapy in MTC, Eric Sherman notes. Traditionally, MTC has been considered to be resistant to chemotherapy; however, new research suggests combination strategies may be effective. In some cases, treatment with intravenous 5-fluorouracil plus carboplatin results high responses with fewer toxicity than TKIs, states Eric Sherman. Additionally, researchers are also examining treatment with temozolomide and capecitabine.
There are currently several clinical trials examining treatments for patients with MTC, which was not the case a few years ago, explains Steven I. Sherman, MD. Additionally, the evaluation of preclinical evidence and biologic mechanisms has helped researchers develop more effective approaches. However, biopsy-driven clinical trials that provide data on biology are becoming more difficult to conduct, explains Steven Sherman. To address this, the International Thyroid Oncology Group is attempting to enhance the quality of trials to yield information on the biology of the disease and the mechanisms of action for the drugs, Steven Sherman notes.