Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma Journal Article
| Authors: | Sherman, E. J.; Su, Y. B.; Lyall, A.; Schoder, H.; Fury, M. G.; Ghossein, R. A.; Haque, S.; Lisa, D.; Shaha, A. R.; Tuttle, R. M.; Pfister, D. G. |
| Article 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. © 2013, Mary Ann Liebert, Inc. |
| Keywords: | adult; protein expression; treatment response; aged; middle aged; survival analysis; overall survival; constipation; drug tolerability; fatigue; cancer growth; drug safety; systemic therapy; positron emission tomography; recurrent cancer; follow-up studies; radiopharmaceuticals; computer assisted tomography; phase 2 clinical trial; nausea; vomiting; qt prolongation; hemoglobin; in vivo study; antineoplastic activity; histology; alanine aminotransferase blood level; aspartate aminotransferase blood level; dyspnea; lymphocytopenia; lung embolism; alanine aminotransferase; aspartate aminotransferase; drug fatality; dysphagia; radioactive iodine; drug uptake; iodine radioisotopes; whole body imaging; messenger rna; carcinoma; taste disorder; histone deacetylase inhibitors; thyroid carcinoma; thyroid neoplasms; heartburn; thyroglobulin; thyroglobulin blood level; thyroid gland; antibiotics, antineoplastic; dyspepsia; romidepsin; recombinant thyrotropin; depsipeptides; radiation tolerance; thyroid follicular carcinoma; sudden death; sodium iodide symporter; thyroid parafollicular cell; thyroglobulin antibody; radioactive iodine refractory thyroid carcinoma |
| Journal Title: | Thyroid |
| Volume: | 23 |
| Issue: | 5 |
| ISSN: | 1050-7256 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2013-05-01 |
| Start Page: | 593 |
| End Page: | 599 |
| Language: | English |
| DOI: | 10.1089/thy.2012.0393 |
| PROVIDER: | scopus |
| PMCID: | PMC3643228 |
| PUBMED: | 23186033 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2013" - "CODEN: THYRE" - "Source: Scopus" |
