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Phase II Study of Safety and Efficacy of Motesanib in Patients With Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer
Abstract
Purpose: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). Patients and Methods: Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers. Results: Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease ≥ 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target lesion measurement. Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum calcitonin and carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related adverse events were diarrhea (41%), fatigue (41%), hypothyroidism (29%), hypertension (27%), and anorexia (27%). In pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated thyroid cancer patients from the same study. Conclusion: Although the objective response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib.
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“The need for a substantially increased dose of LT4 has been reported in athyreotic patients prescribed tyrosine kinase inhibitors such as imatinib (188), motesanib (189), sorafenib (190), sunitinib, and vandetanib (191).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [189]
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Metadata
- Authors
- Schlumberger, M. J., Elisei, R., Bastholt, L., Wirth, L. J., Martins, R. G., Locati, L. D., Jarzab, B., Pacini, F., Daumerie, C., Droz, J.-P., Eschenberg, M. J., Sun, Y.-N., Juan, T., Stepan, D. E., & Sherman, S. I.
- Affiliations
- University of Siena (IT)
- From the Institut Gustave Roussy, University Paris Sud, Villejuif; Centre Léon Bérard, Lyon, France; University of Pisa, Pisa; Istituto Nazionale dei Tumori, Milan; University of Siena, Siena, Italy; Odense University Hospital, Odense, Denmark; Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Université Catholique de Louvain, Brussels, Belgium; Head and Neck Oncology, Dana-Farber Cancer Institute, Boston, MA; University of Washington, Seattle, WA; Amgen, Thousand...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2009-08-10
- Volume
- 27
- Issue
- 23
- Pages
- 3794-3801
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2112475888
- Cited by
- 340
- References
- 35
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 14 · 2019: 12 · 2018: 11 · 2017: 14 · 2016: 22 · 2015: 26 · 2014: 38 · 2013: 36 · 2012: 46
- FWCI
- 33.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Keywords
- motesanib, medullary thyroid carcinoma, metastatic thyroid cancer, VEGFR inhibitors, platelet-derived growth factor receptor, KIT inhibitors, tyrosine kinase inhibitors, progression-free survival, stable disease, calcitonin, carcinoembryonic antigen, pharmacokinetics, adverse events, diarrhea, hypothyroidism
- MeSH terms
- Adult, Aged, Antineoplastic Agents, Female, Humans, Indoles, Male, Middle Aged, Niacinamide, Oligonucleotides, Thyroid Neoplasms, Treatment Outcome, Receptors, Platelet-Derived Growth Factor, Carcinoma, Medullary, Proto-Oncogene Proteins c-kit, Receptors, Vascular Endothelial Growth Factor
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