Document Detail


Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma.
MedLine Citation:
PMID:  23186033     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Eric J Sherman; Yungpo Bernard Su; Ashima Lyall; Heiko Schöder; Matthew G Fury; Ronald A Ghossein; Sofia Haque; Donna Lisa; Ashok R Shaha; R Michael Tuttle; David G Pfister
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Thyroid : official journal of the American Thyroid Association     Volume:  23     ISSN:  1557-9077     ISO Abbreviation:  Thyroid     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-30     Completed Date:  2013-11-14     Revised Date:  2014-06-26    
Medline Journal Info:
Nlm Unique ID:  9104317     Medline TA:  Thyroid     Country:  United States    
Other Details:
Languages:  eng     Pagination:  593-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antibiotics, Antineoplastic / adverse effects,  therapeutic use*
Carcinoma / drug therapy*,  physiopathology,  radionuclide imaging,  radiotherapy
Depsipeptides / adverse effects,  therapeutic use*
Female
Follow-Up Studies
Histone Deacetylase Inhibitors / adverse effects,  therapeutic use
Humans
Iodine Radioisotopes / diagnostic use*,  therapeutic use
Male
Middle Aged
Radiation Tolerance
Radiopharmaceuticals / diagnostic use*,  therapeutic use
Survival Analysis
Thyroid Gland / drug effects*,  physiopathology,  radionuclide imaging
Thyroid Neoplasms / drug therapy*,  physiopathology,  radionuclide imaging,  radiotherapy
Whole Body Imaging
Grant Support
ID/Acronym/Agency:
N01 CM 62206/CM/NCI NIH HHS; P30 CA008748/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Depsipeptides; 0/Histone Deacetylase Inhibitors; 0/Iodine Radioisotopes; 0/Radiopharmaceuticals; 128517-07-7/romidepsin
Comments/Corrections

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