Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial
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 MT...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2015/348124 |
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| author | T. C. Schneider D. de Wit T. P. Links N. P. van Erp J. J. M. van der Hoeven H. Gelderblom T. van Wezel R. van Eijk H. Morreau H. J. Guchelaar E. Kapiteijn |
| author_facet | T. C. Schneider D. de Wit T. P. Links N. P. van Erp J. J. M. van der Hoeven H. Gelderblom T. van Wezel R. van Eijk H. Morreau H. J. Guchelaar E. Kapiteijn |
| author_sort | T. C. Schneider |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cfa67ea0c7d54ce4ae61aa60db8aa78c |
| institution | DOAJ |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-cfa67ea0c7d54ce4ae61aa60db8aa78c2025-08-20T03:19:46ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/348124348124Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II TrialT. C. Schneider0D. de Wit1T. P. Links2N. P. van Erp3J. J. M. van der Hoeven4H. Gelderblom5T. van Wezel6R. van Eijk7H. Morreau8H. J. Guchelaar9E. Kapiteijn10Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Endocrinology, University Medical Center Groningen, 9700 RB Groningen, NetherlandsDepartment of Clinical Pharmacy, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, NetherlandsDepartment of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsDepartment of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, NetherlandsObjective. 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.http://dx.doi.org/10.1155/2015/348124 |
| spellingShingle | T. C. Schneider D. de Wit T. P. Links N. P. van Erp J. J. M. van der Hoeven H. Gelderblom T. van Wezel R. van Eijk H. Morreau H. J. Guchelaar E. Kapiteijn Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial International Journal of Endocrinology |
| title | Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial |
| title_full | Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial |
| title_fullStr | Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial |
| title_full_unstemmed | Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial |
| title_short | Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial |
| title_sort | beneficial effects of the mtor inhibitor everolimus in patients with advanced medullary thyroid carcinoma subgroup results of a phase ii trial |
| url | http://dx.doi.org/10.1155/2015/348124 |
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