First experience with proteasome inhibitor treatment of radioiodine nonavid thyroid cancer using bortezomib

Clin Nucl Med. 2012 Jun;37(6):539-44. doi: 10.1097/RLU.0b013e31824c5f24.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Positron-Emission Tomography
  • Protease Inhibitors / therapeutic use*
  • Proteasome Inhibitors*
  • Pyrazines / therapeutic use*
  • Quality of Life
  • Thyroid Neoplasms / diagnostic imaging
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / radiotherapy*
  • Treatment Failure

Substances

  • Boronic Acids
  • Iodine Radioisotopes
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Pyrazines
  • Fluorodeoxyglucose F18
  • Bortezomib