Evidence map›Paper›PMID 25920375›Full record

Trial reportJournal of cancer research and clinical oncology2015

Epstein-Barr virus-targeted therapy in nasopharyngeal carcinoma.

Sharon D Stoker, Zlata Novalić, Maarten A Wildeman, Alwin D R Huitema, Sandra A W M Verkuijlen, Hedy Juwana, Astrid E Greijer, I Bing Tan, Jaap M Middeldorp, Jan Paul de Boer

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of cancer research and clinical oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02761291 (Phase I Study of Cytolytic Viral Activation Therapy), which is not on this map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.3field-weighted citation impact, top 6% 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.

NCT02761291 phase1unknown statusnot on this mapstarted 2016, after this paper: background citation

Phase I Study of Cytolytic Viral Activation Therapy (CVAT) for Recurrent/Metastatic Nasopharyngeal Carcinoma

TypeinterventionalSponsorChang Gung Memorial HospitalRan2016Enrolled18ConditionsNasopharyngeal CarcinomaArmsGemcitabine, Valproic acid, Valganciclovir
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 51 citations in OpenAlex.

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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

10 authors at 4 institutions in 3 countries.

Sharon D StokerDepartment of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands, s.stoker@nki.nl.
Zlata Novalić
Maarten A Wildeman
Alwin D R Huitema
Sandra A W M Verkuijlen
Hedy Juwana
Astrid E Greijer
I Bing Tan
Jaap M Middeldorp
Jan Paul de Boer
Amsterdam UMC Location VUmc · NLThe Netherlands Cancer Institute · NLADA University · AZOncode Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDespite successful primary treatment of nasopharyngeal carcinoma (NPC), the incidence of distant metastasis remains 25-34 %. Treatment options are limited, and survival is poor. Intratumoural Epstein-Barr virus (EBV) was used as treatment target. In NPC, EBV is present in a latent state, expressing only few non-immunogenic viral products. Gemcitabine and valproic acid can trigger EBV to the lytic state, wherein viral kinases are expressed, making EBV-positive tumour cells susceptible for antiviral therapy with, i.e. valganciclovir, and inducing an EBV-specific immune response.

methodsThis drug combination was applied in eight patients with EBV-positive NPC, refractory to conventional treatment. The primary endpoints were safety, tolerability and clinical response. Secondary endpoint was to get proof of concept based on biomarkers, i.e. pharmacokinetics, EBV-DNA load in whole blood and nasopharyngeal brushes, EBV-RNA profiling for proof of lytic induction, EBV-IgG and EBV-IgA levels and diversity and EBV-specific T cell response.

resultsThe best observed clinical response was partial in two patients (25 %) and stable disease in three patients (37.5 %). The median survival was 9 months (95 % confidence interval 7-17 months). Effective dose levels were reached. Peaking of EBV-DNA loads in blood and brush proved the biological effect on EBV during most treatment cycles. In one patient, RNA profiling confirmed lytic EBV induction. EBV-IgG and EBV-IgA antibody levels were already high before treatment and did not change during treatment. No changes in EBV-specific T cell response were detected.

conclusionThe treatment was safe with manageable side effects, clinical response was observed, and viral activation corroborated.

Indexed as

AdultAntibodies, ViralAntineoplastic Combined Chemotherapy ProtocolsCarcinomaDeoxycytidineDNA, ViralFemaleGemcitabineHerpesvirus 4, HumanHumansImmunoglobulin AImmunoglobulin GMaleMiddle AgedNasopharyngeal CarcinomaNasopharyngeal NeoplasmsAntibodies, ViralDeoxycytidineDNA, ViralGemcitabineImmunoglobulin AImmunoglobulin GValproic Acid

Identifiers

PMID25920375
PMCPMC11823716
OpenAlexW1992103364

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.