ArticlePloS one2018
A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02532114 (A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer), which is not on this map. Cited by 90 papers, 2 of them syntheses that pooled 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.
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.
A Phase I Study of Niclosamide in Combination With Enzalutamide in Men With Castration-Resistant Prostate Cancer
Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Niclosamide as a Promising Therapeutic Player in Human Cancer and Other Diseases.International journal of molecular sciences · 2022Pooled it
- Androgen receptor variant-driven prostate cancer II: advances in clinical investigation.Prostate cancer and prostatic diseases · 2020Pooled it
- Trial
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- Discovery of Niclosamide Analogs with Potent Mitochondrial Uncoupling Activity and Reduced Mitochondrial Inhibition-Associated Toxicity.ACS medicinal chemistry letters · 2026Article
- Rafoxanide disrupts mitochondrial homeostasis through VDAC1 modulation in colorectal cancer cells.Cell death discovery · 2026Article
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- How Can Pharmacology Help Us Overcome the Challenges of Drug Repositioning as Antivirals to Treat Emerging Pathogens? The Example of Covid-19.Clinical and translational science · 2026Review
- Toxicities of novel androgen receptor pathway inhibitor targeted therapies in advanced prostate cancer.Current opinion in urology · 2025Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Valine-Niclosamide for Treatment of Androgen Receptor Splice Variant-Positive Hepatocellular Carcinoma.Cancers · 2025Article
- Repurposing Rafoxanide: From Parasite Killer to Cancer Fighter.Biomedicines · 2025Review
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Androgen receptor inhibitors in treating prostate cancer.Asian journal of andrology · 2025Review
- Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.Cell reports. Medicine · 2025Article
- Off-target effects of mitochondrial oxidative phosphorylation inhibitors are common and can compromise the viability of cultured cells.Mitochondrial communications · 2025Article
- Therapeutic Potential of Natural Compounds to Modulate WNT/β-Catenin Signaling in Cancer: Current State of Art and Challenges.International journal of molecular sciences · 2024Review
- Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology.Cancers · 2024Review
- TMEM16 proteins: CaInternational journal of molecular medicine · 2024Review
- Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture.Chemosphere · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundNiclosamide, an FDA-approved anti-helminthic drug, has activity in preclinical models of castration-resistant prostate cancer (CRPC). Potential mechanisms of action include degrading constitutively active androgen receptor splice variants (AR-Vs) or inhibiting other drug-resistance pathways (e.g., Wnt-signaling). Published pharmacokinetics data suggests that niclosamide has poor oral bioavailability, potentially limiting its use as a cancer drug. Therefore, we launched a Phase I study testing oral niclosamide in combination with enzalutamide, for longer and at higher doses than those used to treat helminthic infections.
methodsWe conducted a Phase I dose-escalation study testing oral niclosamide plus standard-dose enzalutamide in men with metastatic CRPC previously treated with abiraterone. Niclosamide was given three-times-daily (TID) at the following dose-levels: 500, 1000 or 1500mg. The primary objective was to assess safety. Secondary objectives, included measuring AR-V expression from circulating tumor cells (CTCs) using the AdnaTest assay, evaluating PSA changes and determining niclosamide's pharmacokinetic profile.
results20 patients screened and 5 enrolled after passing all screening procedures. 13(65%) patients had detectable CTCs, but only one was AR-V+. There were no dose-limiting toxicities (DLTs) in 3 patients on the 500mg TID cohort; however, both (N = 2) subjects on the 1000mg TID cohort experienced DLTs (prolonged grade 3 nausea, vomiting, diarrhea; and colitis). The maximum plasma concentration ranged from 35.7 to 182 ng/mL and was not consistently above the minimum effective concentration in preclinical studies. There were no PSA declines in any enrolled subject. Because plasma concentrations at the maximum tolerated dose (500mg TID) were not consistently above the expected therapeutic threshold, the Data Safety Monitoring Board closed the study for futility.
conclusionsOral niclosamide could not be escalated above 500mg TID, and plasma concentrations were not consistently above the threshold shown to inhibit growth in CRPC models. Oral niclosamide is not a viable compound for repurposing as a CRPC treatment. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov: NCT02532114.
Indexed as
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.