Evidence map›Paper›PMID 28186961›Full record

Trial reportOncotarget2017

Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.

Nilofer S Azad, Anthony El-Khoueiry, Jun Yin, Ann L Oberg, Patrick Flynn, Douglas Adkins, Anup Sharma, Daniel J Weisenberger, Thomas Brown, Prakriti Medvari and 14 more

Open access · diamondAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.5field-weighted citation impact, top 5% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 91 citations in OpenAlex.

  1. Trial
  2. Trial
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  4. Trial
  5. Targeting the Epigenome in Colorectal Cancer.International journal of molecular sciences · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Sterile activation of RNA-sensing pathways in autoimmunity.Journal of molecular cell biology · 2024
    Review
  14. Article
  15. Review
  16. Preclinical Evaluation of NTX-301, a Novel DNA Hypomethylating Agent in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  17. Review
  18. Article
  19. Article
  20. Article
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

24 authors at 8 institutions in 1 country.

Nilofer S AzadJohns Hopkins University, Baltimore, MD, USA.
Anthony El-KhoueiryUniversity of Southern California, Los Angeles, CA, USA.
Jun YinMayo Clinic, Rochestor, MN, USA.
Ann L ObergMayo Clinic, Rochestor, MN, USA.
Patrick FlynnMetro-Minnesota CCOP, Minneapolis, MN, USA.
Douglas AdkinsWashington University, St. Louis, MO, USA.
Anup SharmaJohns Hopkins University, Baltimore, MD, USA.
Daniel J WeisenbergerUniversity of Southern California, Los Angeles, CA, USA.
Thomas BrownJohns Hopkins University, Baltimore, MD, USA.
Prakriti MedvariJohns Hopkins University, Baltimore, MD, USA.
Peter A JonesVan Andel Research Institute, Grand Rapids, MI, USA.
Hariharan EaswaranJohns Hopkins University, Baltimore, MD, USA.
Ihab KamelJohns Hopkins University, Baltimore, MD, USA.
Nathan BaharyUniversity of Pittsburgh, Pittsburgh, PA, USA.
George KimMayo Clinic, Jacksonville, FL, USA.
Joel PicusWashington University, St. Louis, MO, USA.
Henry C PitotMayo Clinic, Rochestor, MN, USA.
Charles ErlichmanMayo Clinic, Rochestor, MN, USA.
Ross DonehowerJohns Hopkins University, Baltimore, MD, USA.
Hui ShenVan Andel Research Institute, Grand Rapids, MI, USA.
Peter W LairdVan Andel Research Institute, Grand Rapids, MI, USA.
Richard PiekarzWashington University, St. Louis, MO, USA.
Stephen BaylinJohns Hopkins University, Baltimore, MD, USA.
Nita AhujaJohns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USMayo Clinic in Arizona · USVan Andel Institute · USWashington University in St. Louis · USUniversity of Southern California · USMayo Clinic in Florida · USMetro-Minnesota Community Oncology Research Consortium · USUniversity of Pittsburgh · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Phase I Molecular and Clinical Pharmacodynamic Trials ETCTNUM1CA186717 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI A. Dimitrios Colevas, Alexey V. Danilov · 2014 to 2026
$19.8M
NCI NIH HHS P30 CA015083NCI NIH HHS UM1 CA186717
6 · The paper itself

Abstract

purposeTherapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. EXPERIMENTAL

designWe conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy.

resultsForty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median.

conclusionIn this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsAzacitidineBenzamidesCell Line, TumorCohort StudiesColorectal NeoplasmsDNA MethylationDrug Administration ScheduleEpigenesis, GeneticFemaleHCT116 CellsHumansMaleMiddle AgedAzacitidineBenzamidesentinostatPyridinescolorectal cancerDNA methyltransferases inhibitorsepigeneticshistone deacetylase inhibitors

Identifiers

PMID28186961
PMCPMC5471058
OpenAlexW2587153246

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.