title: Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results of a Phase II Clinical Trial.
abstract: Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer.
  
  
  
  Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily. The primary endpoint was disease control rate [complete (CR) + partial response (PR) + stable disease (SD) > 24 weeks]. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and mutational and pharmacokinetic-related outcomes.
  
  
  
  Median follow-up duration was 38 months (2-64). Seventeen patients (65%) showed SD, of which 15 (58%) showed SD >24 weeks. No CR or PR was observed. Median PFS and OS were 9 [95% confidence interval (CI): 4 to 14] and 18 (95% CI: 7 to 29) months, respectively. Survival was negatively influenced by the presence of bone metastases. Toxicity was predominantly grade 1/2 and included anemia (64%), cough (64%), stomatitis (61%), and hyperglycemia (61%). Duration of SD was related to everolimus exposure. The presence of somatic gene variants related to mTOR signaling did not clearly stratify for responses.
  
  
  
  Everolimus has clinically relevant antitumor activity in patients with advanced differentiated thyroid cancer. Given the observed disease control rate and the relatively low toxicity profile, further investigation of everolimus in sequential or combination therapy in these patients is warranted.
authors.affiliation: Departments of Clinical Oncology.|Pathology, and.
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Schneider
authors.affiliation: Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
authors.forename: Djoeke
authors.initials: D
authors.lastname: de Wit
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9713 GZ, The Netherlands; and.
authors.forename: Thera P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Department of Clinical Pharmacy, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Nielka P
authors.initials: NP
authors.lastname: van Erp
authors.affiliation: Departments of Clinical Oncology.
authors.forename: Jakobus J M
authors.initials: JJ
authors.lastname: van der Hoeven
authors.affiliation: Departments of Clinical Oncology.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Departments of Clinical Oncology.
authors.forename: Inge C F M
authors.initials: IC
authors.lastname: Roozen
authors.affiliation: Departments of Clinical Oncology.
authors.forename: Manon
authors.initials: M
authors.lastname: Bos
authors.affiliation: Pathology, and.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Corver
authors.affiliation: Pathology, and.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Clinical Pharmacy, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
authors.forename: Jan W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Pathology, and.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.affiliation: Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Departments of Clinical Oncology.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068338:Everolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus