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Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid

Elizabeth Fox1, Brigitte C Widemann, Meredith K Chuk

  • 1Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. foxe@email.chop.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 15, 2013
PubMed
Abstract

Insights

Vandetanib is an effective treatment for pediatric medullary thyroid carcinoma (MTC) associated with MEN2B. This study found the drug to be well-tolerated and active in children and adolescents with advanced MTC.

Area of Science:

  • Pediatric Oncology
  • Molecular Genetics
  • Pharmacology

Background:

  • Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor often linked to Multiple Endocrine Neoplasia type 2 (MEN2) syndromes.
  • Germline activating mutations in the RET proto-oncogene are the primary cause of MEN2-associated MTC.
  • Vandetanib, an inhibitor of VEGF and EGF receptor kinases, has demonstrated activity in adult MTC by blocking RET tyrosine kinase.

Purpose of the Study:

  • To determine a recommended dose of vandetanib for pediatric patients with MTC.
  • To assess the antitumor activity of vandetanib in children and adolescents with MTC.
  • To evaluate the safety and tolerability of vandetanib in this population.

Main Methods:

  • A Phase I/II clinical trial was conducted involving pediatric patients (5-18 years) with MTC.
  • Vandetanib was administered orally at 100 mg/m(2)/d, with an option to escalate to 150 mg/m(2)/d.
  • Antitumor response was evaluated using RECIST criteria for radiographic changes and by monitoring serum calcitonin and CEA levels for biomarker response.

Main Results:

  • Sixteen pediatric patients with locally advanced or metastatic MTC received vandetanib.
  • The primary dose-limiting toxicity was diarrhea.
  • In patients with M918T RET mutations, the objective partial response rate was 47%, with significant biomarker responses observed for calcitonin and CEA.

Conclusions:

  • Vandetanib at 100 mg/m(2)/d is a well-tolerated and highly active treatment for pediatric patients with MEN2B and advanced MTC.
  • The study highlights the efficacy of targeted therapy based on specific genetic mutations in pediatric cancer.
  • Innovative trial designs can effectively evaluate novel therapies in pediatric oncology populations.

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