Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer

Samuel A. Wells, Jessica E. Gosnell, Robert F. Gagel, Jeffrey Moley, David Pfister, Julie A. Sosa, Michael Skinner, Annetta Krebs, James Vasselli, Martin Schlumberger

Research output: Contribution to journalArticle

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Abstract

Purpose: There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. Methods: Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results: Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at ≥ 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). Conclusion: In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

Original languageEnglish (US)
Pages (from-to)767-772
Number of pages6
JournalJournal of Clinical Oncology
Volume28
Issue number5
DOIs
StatePublished - Feb 10 2010

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Therapeutics
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Medullary Thyroid cancer
Vascular Endothelial Growth Factor Receptor
Proto-Oncogenes
Carcinoembryonic Antigen
Calcitonin
Rare Diseases
Exanthema
Serum
Epidermal Growth Factor Receptor
Nausea
Fatigue
Disease Progression
Diarrhea
Phosphotransferases
Research Personnel
Neoplasm Metastasis
Mutation
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Wells, S. A., Gosnell, J. E., Gagel, R. F., Moley, J., Pfister, D., Sosa, J. A., ... Schlumberger, M. (2010). Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. Journal of Clinical Oncology, 28(5), 767-772. https://doi.org/10.1200/JCO.2009.23.6604

Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. / Wells, Samuel A.; Gosnell, Jessica E.; Gagel, Robert F.; Moley, Jeffrey; Pfister, David; Sosa, Julie A.; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin.

In: Journal of Clinical Oncology, Vol. 28, No. 5, 10.02.2010, p. 767-772.

Research output: Contribution to journalArticle

Wells, SA, Gosnell, JE, Gagel, RF, Moley, J, Pfister, D, Sosa, JA, Skinner, M, Krebs, A, Vasselli, J & Schlumberger, M 2010, 'Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer', Journal of Clinical Oncology, vol. 28, no. 5, pp. 767-772. https://doi.org/10.1200/JCO.2009.23.6604
Wells, Samuel A. ; Gosnell, Jessica E. ; Gagel, Robert F. ; Moley, Jeffrey ; Pfister, David ; Sosa, Julie A. ; Skinner, Michael ; Krebs, Annetta ; Vasselli, James ; Schlumberger, Martin. / Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 5. pp. 767-772.
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abstract = "Purpose: There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. Methods: Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results: Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20{\%} of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53{\%} of patients (ie, 16 of 30 patients) experienced stable disease at ≥ 24 weeks, which yielded a disease control rate of 73{\%} (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50{\%} or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70{\%}), rash (67{\%}), fatigue (63{\%}), and nausea (63{\%}). Conclusion: In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.",
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AU - Pfister, David

AU - Sosa, Julie A.

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N2 - Purpose: There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. Methods: Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results: Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at ≥ 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). Conclusion: In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

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