Evidence map›Paper›PMID 33574900›Full record

ArticleEcancermedicalscience2020

Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers.

Milena Perez Mak, Fatima Solange Pasini, Lixia Diao, Fabyane O Teixeira Garcia, Tiago Kenji Takahashi, Denyei Nakazato, Renata Eiras Martins, Cristiane Maria Almeida, Marco Aurelio Vamondes Kulcsar, Valdelania Aparecida Lamounier and 9 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Ecancermedicalscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01695122 (Efficacy Evaluation of the Combination of Valproic Acid and Standard Platinum-based Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 25% 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.

NCT01695122 phase2completednot on this map

Efficacy Evaluation of the Combination of Valproic Acid and Standard Platinum-based Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

TypeinterventionalSponsorInstituto do Cancer do Estado de São PauloRan2012 to 2014Enrolled14ConditionsHead and Neck Cancer, Oral Cavity Cancer, Oropharyngeal CancerArmsValproic Acid
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025
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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

19 authors at 3 institutions in 2 countries.

Milena Perez MakDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Fatima Solange PasiniCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Lixia DiaoDepartment of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, 1400 Pressler St. Floor 4, FCT4.6000, Houston, Texas, USA.
Fabyane O Teixeira GarciaCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Tiago Kenji TakahashiDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Denyei NakazatoDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Renata Eiras MartinsDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Cristiane Maria AlmeidaDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Marco Aurelio Vamondes KulcsarHead and Neck Surgery Department, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Valdelania Aparecida LamounierDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Emily Montosa NunesCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Isabela Cristina de SouzaCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Marcio Ricardo Taveira GarciaDepartment of Radiology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Alex Vieira AmadioDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Sheila Aparecida C SiqueiraDepartment of Pathology, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Eneas de Carvalho Aguiar, 255, CEP 05403-000, Sao Paulo, SP, Brazil.
Igor Moysés Longo SnitcovskyCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Laura SicheroCenter for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Jing WangHead and Neck Surgery Department, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Gilberto de CastroDepartment of Medical Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo, 251 12th floor, CEP 01246-000, Sao Paulo, SP, Brazil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo · BRInstituto do Câncer do Estado de São Paulo · BRThe University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCisplatin-based chemoradiation (CCRT) offers locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients high local control rate, however, relapses are frequent. Our goal was to evaluate if association of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with CCRT improved response rate (RR) and associated biomarkers.

methodsThis phase II trial included patients with unresectable locally advanced (LA) oropharynx (OP) squamous cell carcinoma. CCRT began after 2 weeks of VPA (P1). Primary goal was RR at 8 weeks after chemoradiation (CRT)+VPA (P2). Biomarkers included microRNA (miR) polymerase chain reaction (PCR)-array profiling in plasma compared to healthy controls by two-sample t-test. Distribution of p-values was analysed by beta-uniform mixture. Findings were validated by real-time PCR quantitative polymerase chain reaction (qPCR) for selected miRs in plasma and saliva. p16, HDAC2 and RAD23 Homolog B, Nucleotide Excision Repair Protein (HR23B) tumour immunohistochemistry were evaluated.

resultsGiven significant toxicities, accrual was interrupted after inclusion of ten LA p16 negative OP patients. All were male, smokers/ex-smokers, aged 41-65 and with previous moderate/high alcohol intake. Nine evaluable patients yielded a RR of 88%. At false discovery rate of 5%, 169 miRs were differentially expressed between patients and controls, including lower expression of tumour suppressors (TSs) such as miR-31, -222, -let-7a/b/e and -145. miR-let-7a/e expression was validated by qPCR using saliva. A HDAC2 H-score above 170 was 90% accurate in predicting 6-month disease-free survival.

conclusionsVPA and CRT offered high RR; however, with prohibitive toxicities, which led to early trial termination. Patients and controls had a distinct pattern of miR expression, mainly with low levels of TS miRs targeting Tumor protein P53 (TP53). miR-let-7a/e levels were lower in patients compared to controls, which reinforces the aggressive nature of such tumours (NCT01695122).

Indexed as

chemoradiationepigeneticshead and neck cancermicroRNAvalproic acid

Identifiers

PMID33574900
PMCPMC7864693
OpenAlexW3112135152

What OpenQuestion holds

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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.