Originally published as JCO Early Release 10.1200/JCO.2008.18.7815 on June 29 2009

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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

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 Skodowska-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 Oaks, CA; and The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Corresponding author: Martin Schlumberger, MD, Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cédex, France; e-mail: martin.schlumberger{at}igr.fr.

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.

Supported by Amgen, Thousand Oaks, CA.

Presented in part at the 89th Annual Meeting of the Endocrine Society, June 2-5, 2007, Toronto, ON, Canada; and the 32nd Annual Meeting of the European Thyroid Association, September 1-5, 2007, Leipzig, Germany.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00121628 [ClinicalTrials.gov] .

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