ArticleCancer chemotherapy and pharmacology2014
Phase I study of anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers.
Article in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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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.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Epigenetic modulation to overcome immune suppression in pancreatic cancer.Clinical epigenetics · 2026Review
- Epigenetic marvels: exploring the landscape of colorectal cancer treatment through cutting-edge epigenetic-based drug strategies.Clinical epigenetics · 2025Review
- Sodium channel-inhibiting drugs and cancer-specific survival: a population-based study of electronic primary care data.BMJ open · 2023Article
- Aberrations in ion channels interacting with lipid metabolism and epithelial-mesenchymal transition in esophageal squamous cell carcinoma.Frontiers in molecular biosciences · 2023Article
- From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.Cancers · 2022Review
- Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.Signal transduction and targeted therapy · 2022Review
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Review
- Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022Review
- The Role of Epigenetic Change in Therapy-Induced Neuroendocrine Prostate Cancer Lineage Plasticity.Frontiers in endocrinology · 2022Review
- Potential of histone deacetylase inhibitors in the control and regulation of prostate, breast and ovarian cancer.Frontiers in chemistry · 2022Review
- Imaging assisted evaluation of antitumor efficacy of a new histone deacetylase inhibitor in the castration-resistant prostate cancer.European journal of nuclear medicine and molecular imaging · 2021Article
- Role of hypoxia in inhibiting dendritic cells by VEGF signaling in tumor microenvironments: mechanism and application.American journal of cancer research · 2021Review
- Review
- Randomized phase II study of valproic acid in combination with bevacizumab and oxaliplatin/fluoropyrimidine regimens in patients withTherapeutic advances in medical oncology · 2020Article
- LPCAT1 enhances castration resistant prostate cancer progression via increased mRNA synthesis and PAF production.PloS one · 2020Article
- Valproic acid combined with cisplatin-based chemoradiation in locally advanced head and neck squamous cell carcinoma patients and associated biomarkers.Ecancermedicalscience · 2020Article
- Sodium valproate and 5-aza-2'-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells.Scientific reports · 2019Article
- Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies.World journal of stem cells · 2019Review
- Clinical development of targeted and immune based anti-cancer therapies.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAnti-angiogenic agents combined with histone deacetylase inhibitors act synergistically in vitro and in vivo. We conducted a phase I study of the combination of the anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers.
methodsBevacizumab was administered at escalating dosages of 2.5-11 mg/kg on days 1 and 15, and oral valproic acid at dosages of 5.3-10 mg/kg on days 1-28 every 28 days to determine the maximum tolerated dose. Pharmacodynamic parameters were assessed in peripheral blood mononuclear cells (histone H3 acetylation) and serum (valproic acid levels).
resultsFifty-seven patients were enrolled. Dose-limiting toxicities were grade 3 altered mental status (n = 2), related to valproic acid. Bevacizumab 11 mg/kg given on days 1 and 15 and valproic acid 5.3 mg/kg daily were the recommended phase II dosages. Stable disease (SD) ≥6 months was reported in 4/57 (7 %) of patients, including two patients with colorectal cancer who had progressed previously on bevacizumab. Of the 39 patients evaluated for histone acetylation, 2 of 3 (67 %) patients with SD ≥6 months showed histone acetylation, while 8 of 36 (22 %) without SD ≥6 months demonstrated histone acetylation (p = 0.16). Patients with any grade of hypertension, compared to others, had a prolonged median survival (11.1 vs. 5.8 months; p = 0.012).
conclusionsThe combination of bevacizumab 11 mg/kg and valproic acid 5.3 mg/kg is safe in patients with advanced malignancies, with activity in colorectal, gastroesophageal junction, and prostate cancer. Patients with hypertension had improved overall survival.
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