Abstract
Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour effects in different types of neuroendocrine tumours, has never been evaluated in patients with medullary thyroid cancer (MTC). The aim of this study was to evaluate the in vitro and in vivo effects of everolimus in combination with octreotide in MTC. Two patients with progressive metastatic MTC and high calcitonin levels were treated with everolimus 5–10 mg/day. Both patients were under treatment with octreotide LAR at the study entry. An in vitro study was also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1 cells). A tumour response was observed in both patients. Serum calcitonin decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells, everolimus induced a significant dose-dependent inhibition in cell proliferation. This effect seems to be related to a cell cycle arrest in G0/G1 phase in both cell lines and to the induction of cellular senescence in TT cells. Everolimus in combination with octreotide may be active as anti-tumour therapy in patients with progressive metastatic MTC, suggesting to further evaluate this agent in MTC patients in a large prospective study.
Highlights
Medullary thyroid cancer (MTC) is a neuroendocrine tumour originating from the C cells within the thyroid gland [1, 2]
Everolimus (RAD001), a novel agent that antagonizes mTOR, has Medullary thyroid cancer may be an optimal model to evaluate the efficacy of everolimus for different reasons: (a) this tumour expresses the specific molecular pathway targeted by everolimus; (b) newly discovered rearranged during transfection (RET) and VEGF inhibitors are under evaluation in clinical trials and promises to be effective in these patients
Because the third month of treatment, everolimus was given at the dose of 10 mg a day resulting in a progressive decrease of calcitonin until the 5month follow-up
Summary
Medullary thyroid cancer (MTC) is a neuroendocrine tumour originating from the C cells within the thyroid gland [1, 2]. Medullary thyroid cancer may be an optimal model to evaluate the efficacy of everolimus for different reasons: (a) this tumour expresses the specific molecular pathway targeted by everolimus; (b) newly discovered rearranged during transfection (RET) and VEGF inhibitors are under evaluation in clinical trials and promises to be effective in these patients. There is no chemotherapy or biological therapy which is available to effectively treat patients with metastatic or relapsing MTC; (c) calcitonin and carcinoembryonic antigen (CEA) are highly sensitive and specific markers of MTC progression and both can help to reliably evaluate the response to everolimus; (d) a recent in vitro study showed a potent inhibitory effect of everolimus on cell proliferation of MTC cells [18].
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