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Previous Volume 359:31-42 July 3, 2008 Number 1 Next

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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 [ClinicalTrials.gov] .)

Source Information

From the University of Texas M.D. Anderson Cancer Center, Houston (S.I.S.); Dana–Farber Cancer Institute, Boston (L.J.W.); Centre Léon Bérard, Lyon, France (J.-P.D.); Medical School Bern, Bern, Switzerland (M.H.); Odense University Hospital, Odense, Denmark (L.B.); University of Washington, Seattle (R.G.M.); Istituto Nazionale dei Tumori, Milan (L.L.); Amgen, Thousand Oaks, CA (M.J.E., Y.-N.S., T.J., D.E.S.); and Institut Gustave Roussy, University Paris Sud, Villejuif, France (M.J.S.).

Address reprint requests to Dr. Sherman at the Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Unit 435, 1515 Holcombe Blvd., P.O. Box 301402, Houston, TX 77230-1402, or at sisherma{at}mdanderson.org.

Full Text of this Article

Related Letters:

Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer
Diaz-Cano S. J., Sherman S. I., the Motesanib Thyroid Cancer Study Group
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N Engl J Med 2008; 359:2727, Dec 18, 2008. Correspondence

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