PMID- 18854394
OWN - NLM
STAT- MEDLINE
DCOM- 20090212
LR  - 20220317
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 94
IP  - 1
DP  - 2009 Jan
TI  - Lack of therapeutic effect of the histone deacetylase inhibitor vorinostat in 
      patients with metastatic radioiodine-refractory thyroid carcinoma.
PG  - 164-70
LID - 10.1210/jc.2008-1631 [doi]
AB  - CONTEXT: Aberrant histone deacetylase activity is seen in a variety of 
      malignancies, and histone deacetylase inhibitors such as vorinostat have been 
      shown to induce cell death and sensitize cells to cytotoxic chemotherapy in 
      thyroid cancer cell lines. This phase II study was undertaken to assess objective 
      response to vorinostat in patients with advanced thyroid cancer. EXPERIMENTAL 
      DESIGN: A total of 19 patients with differentiated thyroid cancer (n = 16) and 
      medullary thyroid cancer (n = 3) were enrolled in the study. Patients received 
      oral vorinostat at a starting dose of 200 mg twice daily, with dose adjustments 
      allowed as necessary for toxicity. Patients were treated for 2 wk, followed by 1 
      wk off therapy (3-wk cycle) until disease progression or study withdrawal. 
      Responses were measured by Response Evaluation Criteria in Solid Tumors criteria 
      and correlated with tumor markers. RESULTS: No patient achieved a partial or 
      complete response. Median duration of therapy in patients with differentiated 
      thyroid cancer was 17 wk, whereas in medullary thyroid cancer patients it was 25 
      wk. Reasons for termination included progression of disease by RECIST criteria (n 
      = 7), clinical progression (n = 3), and adverse events (AEs) (n = 9). AEs were 
      primarily grade 1-3; no clinical grade 4 or grade 5 events were observed. 
      Clinical grade 3 AEs consisted of fatigue, dehydration, ataxia, pneumonia, 
      bruises, and deep vein thrombosis. Severe thrombocytopenia was seen in seven 
      patients (grade 3, n = 5; grade 4, n = 2) and was associated with minor bleeding 
      or bruises. CONCLUSIONS: Vorinostat at this dose and schedule is not an effective 
      treatment for advanced thyroid cancer.
FAU - Woyach, Jennifer A
AU  - Woyach JA
AD  - Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, 
      USA.
FAU - Kloos, Richard T
AU  - Kloos RT
FAU - Ringel, Matthew D
AU  - Ringel MD
FAU - Arbogast, Daria
AU  - Arbogast D
FAU - Collamore, Minden
AU  - Collamore M
FAU - Zwiebel, James A
AU  - Zwiebel JA
FAU - Grever, Michael
AU  - Grever M
FAU - Villalona-Calero, Miguel
AU  - Villalona-Calero M
FAU - Shah, Manisha H
AU  - Shah MH
LA  - eng
SI  - ClinicalTrials.gov/NCT00134043
GR  - N01CM62207/CA/NCI NIH HHS/United States
GR  - U01 CA076576/CA/NCI NIH HHS/United States
GR  - N01-CM-62207/CM/NCI NIH HHS/United States
GR  - U01 CA76576/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20081014
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Iodine Radioisotopes)
RN  - 58IFB293JI (Vorinostat)
RN  - 9007-12-9 (Calcitonin)
RN  - 9010-34-8 (Thyroglobulin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Calcitonin/blood
MH  - Carcinoembryonic Antigen/analysis
MH  - Carcinoma, Medullary/drug therapy/pathology/radiotherapy
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Female
MH  - *Histone Deacetylase Inhibitors
MH  - Humans
MH  - Hydroxamic Acids/*therapeutic use
MH  - Iodine Radioisotopes/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Thyroglobulin/blood
MH  - Thyroid Neoplasms/*drug therapy/pathology/radiotherapy
MH  - Vorinostat
PMC - PMC2630867
EDAT- 2008/10/16 09:00
MHDA- 2009/02/13 09:00
PMCR- 2010/01/01
CRDT- 2008/10/16 09:00
PHST- 2008/10/16 09:00 [pubmed]
PHST- 2009/02/13 09:00 [medline]
PHST- 2008/10/16 09:00 [entrez]
PHST- 2010/01/01 00:00 [pmc-release]
AID - jc.2008-1631 [pii]
AID - 6252 [pii]
AID - 10.1210/jc.2008-1631 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2009 Jan;94(1):164-70. doi: 10.1210/jc.2008-1631. Epub 
      2008 Oct 14.