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.