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Cited by 470Thyroid Cancer Diagnosis and TreatmentAngiogenesis and VEGF in CancerThyroid and Parathyroid Surgery

Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer

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Sherman, Steven I., Wirth, Lori J., Droz, Jean-Pierre, Hofmann, Michael, Bastholt, Lars, Martins, Renato G., Licitra, Lisa, Eschenberg, Michael J. +4 more·2008·New England Journal of Medicine
DOI 10.1056/nejmoa075853
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Abstract

BACKGROUND: The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT. METHODS: In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration. RESULTS: Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective response rate was 14%. Stable disease was achieved in 67% of the patients, and stable disease was maintained for 24 weeks or longer in 35%; 8% had progressive disease as the best response. The Kaplan-Meier estimate of the median duration of the response was 32 weeks (the lower limit of the 95% confidence interval [CI] was 24; the upper limit could not be estimated because of an insufficient number of events); the estimate of median progression-free survival was 40 weeks (95% CI, 32 to 50). Among the 75 patients in whom thyroglobulin analysis was performed, 81% had decreased serum thyroglobulin concentrations during treatment, as compared with baseline levels. The most common treatment-related adverse events were diarrhea (in 59% of the patients), hypertension (56%), fatigue (46%), and weight loss (40%). CONCLUSIONS: Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive. (ClinicalTrials.gov number, NCT00121628.)

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Research works printed but not linked: 4

  1. AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995. Cancer 1998;83:2638-48.
  2. Cooper DS, Doherty GM, Haugen BR, 4. et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2006;16:109-42.
  3. Gottlieb JA, Hill CS Jr. Chemotherapy 16. The New England Journal of Medicine Downloaded from nejm.org on August 29, 2023. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved. n engl j med 359;
  4. Sisson JC, Giordano TJ, Jamadar DA, 24. et al. 131-I treatment of micronodular pulmonary metastases from papillary thy- roid carcinoma. Cancer 1996;78:2184-92.

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Authors
Sherman, S. I., Wirth, L. J., Droz, J.-P., Hofmann, M., Bastholt, L., Martins, R. G., Licitra, L., Eschenberg, M. J., Sun, Y.-N., Juan, T., Stepan, D. E., & Schlumberger, M. J.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Dana-Farber Cancer Institute (US)
  • Centre Léon Bérard (FR)
  • University of Bern (CH)
  • Odense University Hospital (DK)
  • University of Washington (US)
  • Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
  • Amgen (United States) (US)
  • Institut Gustave Roussy (FR)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2008-07-03
Volume
359
Issue
1
Pages
31-42
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa075853
OpenAlex
W2070563197
Cited by
470
References
30
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 15 · 2018: 12 · 2017: 19 · 2016: 28 · 2015: 42 · 2014: 50 · 2013: 34 · 2012: 40
FWCI
44.76
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • BORIS (University Library Bern) (submittedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Amgen
  • Bristol-Myers Squibb
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • Exelixis
  • Eisai
  • Associazione Italiana per la Ricerca sul Cancro
  • Genentech
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
differentiated thyroid cancer, papillary thyroid carcinoma, VEGFR inhibitors, platelet-derived growth factor receptor, KIT inhibitors, metastatic thyroid cancer, objective response rate, progression-free survival, serum thyroglobulin, diarrhea, hypertension
MeSH terms
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Papillary, Female, Genotype, Humans, Indoles, Male, Middle Aged, Niacinamide, Oligonucleotides, Thyroglobulin, Thyroid Neoplasms, Survival Analysis, Adenoma, Oxyphilic, Adenocarcinoma, Follicular, Proto-Oncogene Proteins c-kit, Receptors, Vascular Endothelial Growth Factor

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