title: Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma.
abstract: BACKGROUND
  Historically, systemic therapy for radioactive iodine (RAI)-refractory thyroid cancer has been understudied. Available drugs have modest efficacy. Romidepsin is a histone deacetylase inhibitor with potent antitumor effects both in vitro and in vivo. In thyroid cancer cell lines, romidepsin increases expression of both thyroglobulin and the sodium iodide symporter messenger RNAs, suggesting the possibility of improved iodine concentrating ability of RAI-resistant tumors.
  
  
  METHODS
  This was a single-institution Simon 2-stage phase II clinical study. Eligible patients had progressive, RAI-refractory, recurrent/metastatic, nonmedullary, nonanaplastic thyroid cancer. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 measurable disease and adequate organ/marrow function were required. Romidepsin 13 mg/m² was administered intravenously on days 1, 8, and 15, in cycles of 28 days. The primary endpoint was the response rate by RECIST; change in RAI avidity was a secondary endpoint. The study closed after the first stage due to the lack of response.
  
  
  RESULTS
  Twenty patients were enrolled: female, 50%; median age, 64 years; histology, 8 papillary/1 follicular/11 Hürthle. Grade 4-5 adverse events (AEs) possibly related to the drug: grade 5, 1 sudden death; grade 4, 1 pulmonary embolus. Twelve of 20 subjects had a reported adverse event. No RECIST major responses have been seen. Response per protocol: stable disease, 13; disease progression, 7. Restoration of RAI avidity was documented in two patients. Median overall survival and time on study was 33.2 (1-71+) and 1.7 (0.46-12) months, respectively.
  
  
  CONCLUSIONS
  We observed preliminary signs of in vivo reversal of RAI resistance after treatment with romidepsin. However, no major responses were observed and accrual was poor after the grade 5 AE.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center , New York, NY 10065, USA. shermane@mskcc.org
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sherman
authors.forename: Yungpo Bernard
authors.initials: YB
authors.lastname: Su
authors.forename: Ashima
authors.initials: A
authors.lastname: Lyall
authors.forename: Heiko
authors.initials: H
authors.lastname: Schöder
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Fury
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: Sofia
authors.initials: S
authors.lastname: Haque
authors.forename: Donna
authors.initials: D
authors.lastname: Lisa
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.forename: David G
authors.initials: DG
authors.lastname: Pfister
mesh_terms: D018249:Adenoma, Oxyphilic; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy; D002291:Carcinoma, Papillary; D047630:Depsipeptides / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016019:Survival Analysis; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy; D051598:Whole Body Imaging
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C087123:romidepsin