Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer - PubMed (original) (raw)
Clinical Trial
Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer
Samuel A Wells Jr et al. J Clin Oncol. 2010.
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.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Figures
Fig 1.
Maximum reduction from baseline (or smallest increase from baseline for patients with no reductions) in the sum of the longest diameters of target lesions. The change from baseline in tumor measurement as assessed by investigator review is shown for 29 patients; one non-evaluable patient is not shown. Asterisk indicates patients with a best response of 0% change from baseline (stable disease ≥ 8 weeks but < 24 weeks, n = 1; stable disease ≥ 24 weeks, n = 1). Gray line represents the threshold for partial response (> 30% reduction from baseline sum of longest diameters). Target lesions were defined according to the Response Evaluation Criteria in Solid Tumors (RECIST).
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References
- Schlumberger M, Carlomagno F, Baudin E, et al. New therapeutic approaches to treat medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab. 2008;4:22–32. - PubMed
- Kouvaraki MA, Shapiro SE, Perrier ND, et al. RET proto-oncogene: A review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid. 2005;15:531–544. - PubMed
- Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: Demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107:2134–2142. - PubMed
- Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2:851–856. - PubMed
- Mulligan LM, Kwok JB, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363:458–460. - PubMed
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