Evidence map›Paper›PMID 27392538›Full record

Trial reportClinical endocrinology2017

A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin.

Naris Nilubol, Roxanne Merkel, Lily Yang, Dhaval Patel, James C Reynolds, Samira M Sadowski, Vladimir Neychev, Electron Kebebew

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01182285 phase2completednot on this map

A Phase II Trial of Valproic Acid in Patients With Advanced Thyroid Cancers of Follicular Origin

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2010 to 2016Enrolled13ConditionsThyroid NeoplasmArmsValproic Acid, Liothyronine Sodium
NCT05920512 phase1 / phase2unknown statusnot on this mapstarted 2022, after this paper: background citation

PLA General Hospital

TypeinterventionalSponsorXue-chun LuRan2022 to 2025Enrolled10ConditionsHemophiliaArmsSodium valproate extended-release tablets
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 58 citations in OpenAlex.

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  12. Mechanisms of regulating NIS transport to the cell membrane and redifferentiation therapy in thyroid cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
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  15. Notch Signaling in Thyroid Cancer.Advances in experimental medicine and biology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 3 countries.

Naris NilubolEndocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Roxanne MerkelEndocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lily YangEndocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Dhaval PatelEndocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
James C ReynoldsNuclear Medicine Department, Clinical Research Center, National Institutes of Health, Bethesda, MD, USA.
Samira M SadowskiThoracic and Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland.
Vladimir NeychevDepartment of Surgery, University Multiprofile Hospital for Active Treatment 'Alexandrovska', Medical University, Sofia, Bulgaria.
Electron KebebewEndocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USAlexandrovska Hospital · BGNational Cancer Institute · USNational Institutes of Health Clinical Center · USUniversity Hospital of Geneva · CH

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

objectiveValproic acid (VA) is a histone deacetylase (HDAC) inhibitor that has antiproliferative effects on several types of cancer, including thyroid cancer. In addition, VA has been reported to upregulate the sodium-iodine symporter in thyroid cancer cells and increases radioiodine uptake in preclinical studies. The aim of this study was to assess the antiproliferative effects of VA and to evaluate if VA can increase the radioiodine uptake in patients with advanced, radioiodine-negative thyroid cancer.

designAn open-label Simon two-stage phase II trial. PATIENTS AND MEASUREMENTS: Valproic acid was administered orally, and doses were adjusted to maintain serum trough levels between 50 and 100 mg/l for 10 weeks, followed by injections of recombinant human thyroid-stimulating hormone and a radioiodine uptake scan. Anatomical imaging studies were performed at week 16 to assess tumour response and radioiodine therapy in patients with increased radioiodine uptake.

resultsThirteen patients with a median age of 66 years (50-78 years) were enrolled and evaluated. Seven patients had papillary thyroid cancer (PTC), two had follicular variant PTC, two had follicular thyroid cancer, and two had Hürthle cell carcinoma. None of the 10 patients who completed the 10-week treatment had increased radioiodine uptake at their tumour sites. Three patients were taken off the study prior to the 10-week radioiodine uptake scan: one with grade-3 hepatic toxicity, one with disease progression and one for noncompliance. Four of 13 patients had decreased stimulated serum thyroglobulin with VA treatment. None of the patients had complete or partial responses based on Response Evaluation Criteria in Solid Tumors (RECIST), and six patients had disease progression.

conclusionsValproic acid does not increase radioiodine uptake and does not have anticancer activity in patients with advanced, radioiodine-negative thyroid cancer of follicular cell origin.

Indexed as

Adenocarcinoma, FollicularAgedAged, 80 and overFemaleHistone Deacetylase InhibitorsHumansIodine RadioisotopesMaleMiddle AgedThyroglobulinThyroid NeoplasmsValproic AcidHistone Deacetylase InhibitorsIodine RadioisotopesThyroglobulinValproic Acid

Identifiers

PMID27392538
PMCPMC5581405
OpenAlexW2474627812

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.