ArticleTranslational oncology2014
A Phase I Protocol of Hydralazine and Valproic Acid in Advanced, Previously Treated Solid Cancers.
Article in Translational oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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.
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Epigenetic reprogramming of mast and cancer cells modifies tumor-promoting cytokine networks.Medical oncology (Northwood, London, England) · 2025Article
- The Role of Epigenetic Modifications in Enhancing Bone Marrow Transplantation Efficacy in Cancer.Advances in experimental medicine and biology · 2025Review
- The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.American journal of cancer research · 2024Article
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Article
- Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer.Biomedicines · 2021Article
- Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Wise Management of Ovarian Cancer: On the Cutting Edge.Journal of personalized medicine · 2020Review
- Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy.Scientific reports · 2019Article
- Article
- Comparison of DNA demethylating and histone deacetylase inhibitors hydralazine-valproate versus vorinostat-decitabine incutaneous t-cell lymphoma in HUT78 cells.American journal of blood research · 2018Article
- Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model.Journal of the National Cancer Institute · 2017Article
- The effects of antiepileptic drugs on the growth of glioblastoma cell lines.Journal of neuro-oncology · 2016Article
- Epigenetic modulators as therapeutic targets in prostate cancer.Clinical epigenetics · 2016Review
- Inverse Association between Sodium Channel-Blocking Antiepileptic Drug Use and Cancer: Data Mining of Spontaneous Reporting and Claims Databases.International journal of medical sciences · 2016Article
- Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents.Molecules (Basel, Switzerland) · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Smokers experience aberrant gene promoter methylation in their bronchial cells, which may predispose to the development of neoplasia. Hydralazine is a DNA demethylating agent, and valproic acid is a histone deacetylase inhibitor, and both have modest but synergistic anticancer activity in vitro. We conducted a phase I trial combining valproic acid and hydralazine to determine the maximally tolerated dose (MTD) of hydralazine in combination with a therapeutic dose of valproic acid in patients with advanced, unresectable, and previously treated solid cancers. Twenty females and nine males were enrolled, with a median age of 57 years and a median ECOG performance status of 0. Grade 1 lymphopenia and fatigue were the most common adverse effects. Three subjects withdrew for treatment-related toxicities occurring after the DLT observation period, including testicular edema, rash, and an increase in serum lipase accompanied by hyponatremia in one subject each. A true MTD of hydralazine in combination with therapeutic doses of valproic acid was not reached in this trial, and the planned upper limit of hydralazine investigated in this combination was 400 mg/day without grade 3 or 4 toxicities. A median number of two treatment cycles were delivered. One partial response by Response Evaluation Criteria In Solid Tumors criteria was observed, and five subjects experienced stable disease for 3 to 6 months. The combination of hydralazine and valproic acid is simple, nontoxic, and might be appropriate for chemoprevention or combination with other cancer treatments. This trial supports further investigation of epigenetic modification as a new therapeutic strategy.
Identifiers
What OpenQuestion holds
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.