title: Toxic cardiomyopathy leading to fatal acute cardiac failure related to vandetanib: a case report with histopathological analysis.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) accounts for 3-4% of all malignant thyroid neoplasias. Vandetanib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor 2, epidermal growth factor receptor, and RET, has been approved by the FDA for the treatment of locally advanced or metastatic MTC. The heart seems to be particularly susceptible to adverse effects associated with TKI therapy, and virtually all TKIs have been associated with cardiovascular events.
  
  
  METHODS
  We report the case of a patient with metastatic MTC who was enrolled in the Phase III clinical study (NCT00410761) and presented a favorable response to vandetanib therapy, displaying marked decrease in the level of serologic tumor markers and shrinkage of metastatic lesions. After 14 months of therapy, the patient developed a fatal cardiac failure. Myocardial infarction was excluded by serial measurements of specific cardiac markers (serial troponin-T measurements varied from 0.037 to 0.042 ng/ml) and serologic tests for Chaga's disease were negative. Postmortem examination of the heart revealed cardiomyocyte hypertrophy and marked myocyte degeneration in the subendocardial zones and papillary muscles of the myocardium. These pathological changes are similar to those observed in TKI-treated rats and are suggestive of drug-induced cardiotoxicity.
  
  
  CONCLUSIONS
  This case illustrates a previously unreported serious vandetanib-related adverse effect and highlights the need for close monitoring of patients under TKI therapy in order to identify early signs of congestive heart failure or myocardium damage.
authors.affiliation: Endocrine Division, Thyroid Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rafael Selbach
authors.initials: RS
authors.lastname: Scheffel
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Dora
authors.forename: Débora R
authors.initials: DR
authors.lastname: Siqueira
authors.forename: Lucas Medeiros
authors.initials: LM
authors.lastname: Burttet
authors.forename: Marcelle R
authors.initials: MR
authors.lastname: Cerski
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Maia
mesh_terms: D000328:Adult; D018278:Carcinoma, Neuroendocrine; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000150:complications*; D017326:Clinical Trials, Phase III as Topic; D017809:Fatal Outcome; D005260:Female; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000188:drug therapy
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib