Steven I Sherman

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules ...

BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the treatment of patients with this type of cancer.

METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice ...

BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common histotype among papillary thyroid cancers (PTCs). Although the prognosis of FVPTC is similar to the conventional phenotype, differential diagnostic difficulties may not be uncommon with other follicular thyroid neoplasms, and little is known about their genetic alterations. Defining these alterations may lead to the identification of diagnostic and biologic markers.

METHODS: In this study, ...

PURPOSE: No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy.

EXPERIMENTAL DESIGN: The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR ...

BACKGROUND: Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).

METHODS: In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was ...

BACKGROUND: The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of ...

BACKGROUND: Cabozantinib significantly prolonged progression-free survival (PFS) versus a placebo in patients with progressive, metastatic medullary thyroid cancer (MTC; P < .001). An exploratory analysis of phase 3 trial data evaluated the influence of rearranged during transfection (RET) and RAS (HRAS, KRAS, and NRAS) mutations on cabozantinib clinical activity.

METHODS: Patients (n = 330) were randomized to cabozantinib (140 mg/day) or a placebo. The primary endpoint was PFS. ...

Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib in Japanese patients who participated in SELECT. Outcomes for Japanese patients (lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT ...

BACKGROUND: Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death.

METHODS: The authors reviewed medical records of patients who ...

PURPOSE: Ras/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins.

PATIENTS AND METHODS: We treated 35 patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in a phase I trial. Sorafenib and ...

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines.

METHODS: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence ...

BACKGROUND: About half of patients with papillary thyroid cancer have tumours with activating BRAF(V600E) mutations. Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial. We aimed to establish the activity of vemurafenib in patients with BRAF(V600E)-positive papillary thyroid cancer.

METHODS: We did an open-label, non-randomised, phase 2 trial at ...

PURPOSE: XL184 (cabozantinib) is a potent inhibitor of MET, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, with robust antiangiogenic, antitumor, and anti-invasive effects in preclinical models. Early observations of clinical benefit in a phase I study of cabozantinib, which included patients with medullary thyroid cancer (MTC), led to expansion of an MTC-enriched cohort, which is the focus of this article.

PATIENTS AND METHODS: A phase I dose-escalation study of oral ...