title: Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial: results from a French cohort.
abstract: BACKGROUND
  A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial.
  
  
  METHODS
  Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2).
  
  
  RESULTS
  Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity.
  
  
  CONCLUSIONS
  Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction.
authors: 1 Department of Nuclear Medicine, Hôpital Saint Louis , Paris, France .
authors: Cecile N
authors: CN
authors: Chougnet
authors: Isabelle
authors: I
authors: Borget
authors: Sophie
authors: S
authors: Leboulleux
authors: Christelle
authors: C
authors: de la Fouchardiere
authors: Françoise
authors: F
authors: Bonichon
authors: Lise
authors: L
authors: Criniere
authors: Patricia
authors: P
authors: Niccoli
authors: Stéphane
authors: S
authors: Bardet
authors: Olivier
authors: O
authors: Schneegans
authors: Sylvie
authors: S
authors: Zanetta
authors: Claire
authors: C
authors: Schvartz
authors: Delphine
authors: D
authors: Drui
authors: Bruno
authors: B
authors: Chauffert
authors: Vincent
authors: V
authors: Rohmer
authors: Martin
authors: M
authors: Schlumberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002648:Child; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib