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International Journal of Endocrinology
Volume 2015, Article ID 348124, 8 pages
Clinical Study

Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial

1Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
2Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
3Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
4Department of Endocrinology, University Medical Center Groningen, 9700 RB Groningen, Netherlands
5Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, Netherlands

Received 5 November 2014; Accepted 17 June 2015

Academic Editor: Constantinos Pantos

Copyright © 2015 T. C. Schneider et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors. As part of a prospective phase II study, we analyzed the safety and efficacy of everolimus in advanced MTC. Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included and received everolimus 10 mg daily. The primary objective was determining treatment efficacy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median follow-up duration was 28 weeks (17–147). Five patients (71%) showed SD, of which 4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8–56) and 30 (95%CI: 15–45) weeks, respectively. Toxicity was predominantly grade 1/2 and included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical response was seen in a MEN2A patient. PK characteristics were consistent with phase I data. One patient exhibited extensive toxicity accompanying elevated everolimus plasma concentrations. Conclusions. This study suggests that everolimus exerts clinically relevant antitumor activity in patients with advanced MTC. Given the high level of clinical benefit and the relatively low toxicity profile, further investigation of everolimus in these patients is warranted.