ArticleIntegrative cancer therapies2014
A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.
Article in Integrative cancer therapies, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.Medical oncology (Northwood, London, England) · 2024Pooled it
- Leveraging AI and Natural Compounds: Innovative Approaches in the Diagnosis and Treatment of Hepatocellular Carcinoma.Current pharmaceutical design · 2026Review
- Natural Compounds Targeting MAPK, PI3K/Akt, and JAK/STAT Signaling in Papillary Thyroid Cancer.International journal of molecular sciences · 2025Review
- Isosilybin B: a potential novel therapeutic agent with hepatoprotective, anticancer and antifibrotic properties.Discover oncology · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Milk Thistle (Current medicinal chemistry · 2025Review
- Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications.International journal of nanomedicine · 2025Review
- Novel Strategies Enhancing Bioavailability and Therapeutical Potential of Silibinin for Treatment of Liver Disorders.Drug design, development and therapy · 2024Review
- Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.Endocrine, metabolic & immune disorders drug targets · 2024Article
- The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells.Pharmacological reports : PR · 2023Review
- Long Non-Coding RNAs as Novel Targets for Phytochemicals to Cease Cancer Metastasis.Molecules (Basel, Switzerland) · 2023Review
- Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov.Cancer medicine · 2021Article
- Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Reversing oncogenic transformation with iron chelation.Oncotarget · 2021Review
- Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Plant-derived glucose transport inhibitors with potential antitumor activity.Phytotherapy research : PTR · 2020Review
- Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity.Molecules (Basel, Switzerland) · 2020Review
- Competitive glucose metabolism as a target to boost bladder cancer immunotherapy.Nature reviews. Urology · 2020Review
- Non-coding RNAs: emerging regulators of glucose metabolism in hepatocellular carcinoma.American journal of cancer research · 2020Review
- Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology.Frontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
purposeTo determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. EXPERIMENTAL
designPatients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks.
resultsThree participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug.
conclusionShort-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.
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