title: A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) metastasizes early in its clinical course. No effective systemic therapy is available. Generally (somatic or germline), mutations in the rearranged during transfection gene are considered essential in the pathogenesis of MTC.
  
  
  OBJECTIVE
  We investigated imatinib, a tyrosine kinase inhibitor, as a potential treatment in patients with disseminated MTC.
  
  
  METHODS
  A phase II study was initiated using 600 mg imatinib daily with a possible dose increase to 800 mg in case of progression. Standard Response Evaluation Criteria in Solid Tumors were used using computed tomography or magnetic resonance imaging every 2 months.
  
  
  RESULTS
  There were 15 patients with disseminated MTC treated for up to 12 months. No objective responses were observed. Four patients had stable disease over 24 months. Three patients stopped treatment due to toxic effects [fatigue (n = 2) and nausea (n = 1)]. In four cases the dose of imatinib was decreased because of toxicity [rash and malaise (n = 2) and laryngeal swelling (n = 2)]. Emergency tracheotomy was performed in two cases due to mucosal swelling of the larynx in patients with recurrent nerve palsy and a narrow vocal cleft. In nine patients with a history of a thyroidectomy, the dose of supplemental thyroid hormone was increased because of serious hypothyroidism.
  
  
  CONCLUSIONS
  Imatinib therapy yielded no objective responses and induced considerable toxicity in patients with MTC. A minority of patients had stable disease. Patients with supplemented hypothyroidism or with recurrent nerve palsy are specifically at risk for serious adverse events and need special attention when treated with imatinib.
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 AB Groningen, The Netherlands.
authors.forename: J W B
authors.initials: JW
authors.lastname: de Groot
authors.forename: B A
authors.initials: BA
authors.lastname: Zonnenberg
authors.forename: P Quarles
authors.initials: PQ
authors.lastname: van Ufford-Mannesse
authors.forename: M M
authors.initials: MM
authors.lastname: de Vries
authors.forename: T P
authors.initials: TP
authors.lastname: Links
authors.forename: C J M
authors.initials: CJ
authors.lastname: Lips
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate