title: First experience with proteasome inhibitor treatment of radioiodine nonavid thyroid cancer using bortezomib.
abstract: OBJECTIVE
  Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a poor prognosis. Despite a multimodal therapeutic approach including surgery, chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a high number of TC-associated deaths. The aim of this investigation was to evaluate the response rate of progressive TC patients to treatment with the proteasome inhibitor bortezomib.
  
  
  METHODS
  Seven patients with inoperable, metastasized progressive TC proven to be radioiodine nonavid were included into this pilot study. Patients received bortezomib intravenously with a standardized dose of 1.3 mg/m on days 1, 4, 8, and 11. All patients underwent 3 therapeutic cycles with an interval of 10 days. [F]2-deoxy-2-fluoro-D-glucose positron emission tomography (F-FDG PET) and measurements of thyroglobulin levels were performed before, during, and after therapy, with a 6-week interval to post-therapeutic follow-up.
  
  
  RESULTS
  Stable disease was seen after proteasome inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease of maximum standardized uptake value in both post-therapeutic follow-up investigations, and one of these cases also had decreasing thyroglobulin levels. Two patients experienced stable disease during the posttherapeutic follow-up. Two patients showing a mixed response had an improvement in their clinical situation. One patient had rapidly progressive disease, and died 3 months after the last therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and alterations of the blood count up to WHO (World Health Organization) grade 2 in 5 patients.
  
  
  CONCLUSIONS
  Proteasome inhibitor treatment with bortezomib is a promising therapeutic approach in TC patients without an established treatment alternative. The development of a specific therapeutic regimen for the treatment of radioiodine nonavid TC is warranted.
authors.affiliation: Department of Nuclear Medicine, Innsbruck Medical University, Austria. daniel.putzer@i-med.ac.at
authors.forename: Daniel
authors.initials: D
authors.lastname: Putzer
authors.forename: Micheal
authors.initials: M
authors.lastname: Gabriel
authors.forename: Alexander
authors.initials: A
authors.lastname: Kroiss
authors.forename: Ruth
authors.initials: R
authors.lastname: Madleitner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisterer
authors.forename: Dorota
authors.initials: D
authors.lastname: Kendler
authors.forename: Christian
authors.initials: C
authors.lastname: Uprimny
authors.forename: Reto J
authors.initials: RJ
authors.lastname: Bale
authors.forename: Günther
authors.initials: G
authors.lastname: Gastl
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Virgolini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D011480:Protease Inhibitors / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D011788:Quality of Life; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017211:Treatment Failure
chemical_list: D001897:Boronic Acids; D007457:Iodine Radioisotopes; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D019788:Fluorodeoxyglucose F18; D000069286:Bortezomib