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

  • Wells Jr S
  • Gosnell J
  • Gagel R
 et al. 
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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. © 2010 by American Society of Clinical Oncology.

Author-supplied keywords

  • Administration, Oral
  • Antineoplastic Agents
  • Carcinoma, Medullary
  • Disease-Free Survival
  • Drug Administration Schedule
  • France
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Kaplan Meier method
  • Kaplan-Meiers Estimate
  • N (4 bromo 2 fluorophenyl) 6 methoxy 7 ((1 methylp
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylp
  • Piperidines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-ret
  • QT prolongation
  • Quinazolines
  • RET protein, human
  • Risk Factors
  • Thyroid Neoplasms
  • Time Factors
  • Tumor Markers, Biological
  • United States
  • Young Adult
  • acne
  • adult
  • advanced cancer
  • aged
  • antineoplastic agent
  • article
  • blood
  • bloody diarrhea
  • calcitonin
  • carcinoembryonic antigen
  • clinical article
  • clinical trial
  • creatinine blood level
  • dacarbazine
  • diarrhea
  • disease free survival
  • doxorubicin
  • drug administration
  • drug antagonism
  • drug dose reduction
  • drug efficacy
  • drug withdrawal
  • epidermal growth factor receptor
  • fatigue
  • female
  • genetic predisposition
  • genetics
  • human
  • hypertension
  • inoperable cancer
  • male
  • medullary carcinoma
  • metabolism
  • metastasis
  • middle aged
  • mortality
  • multicenter study
  • mutation
  • nausea
  • oncogene ret
  • open study
  • oral drug administration
  • pathology
  • pedigree
  • phase 2 clinical trial
  • piperidine derivative
  • priority journal
  • protein Ret
  • protein kinase inhibitor
  • quinazoline derivative
  • rash
  • risk factor
  • side effect
  • streptozocin
  • thyroid medullary carcinoma
  • thyroid tumor
  • time
  • treatment duration
  • treatment outcome
  • treatment response
  • tumor marker
  • urea nitrogen blood level
  • vandetanib
  • vasculotropin receptor

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  • S A Wells Jr

  • J E Gosnell

  • R F Gagel

  • J Moley

  • D Pfister

  • J A Sosa

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