Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer

New England Journal of Medicine (Impact Factor: 54.42). 01/2009; 359(25):2727; author reply 2727.
Source: PubMed

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 pro- gressive, 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 radio- graphic review. Additional end points included the duration of the response, pro- gression-free survival, safety, and changes in serum thyroglobulin concentration. Results Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective re- sponse 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. ( number, NCT00121628.)

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Available from: Salvador J Diaz-Cano, Sep 03, 2015
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    • "In recent years, phase II clinical trials of various small molecule tyrosine kinase inhibitors (including sorafenib, motesanib and pazopanib) (Gupta-Abramson et al. 2008; Sherman et al. 2008; Bible et al. 2010) have shown modest activity against thyroid cancers (mainly stabilization disease by RECIST criteria) (Cabanillas et al. 2010). The exact mechanism of action of these agents is still uncertain given the poor correlation between the predicted in vitro targets (e.g., RET and BRAF inhibitors) of these agents, mutational status of the tumors (RET and BRAF mutations ) and clinical response. "
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