Trial reportProstate cancer and prostatic diseases2013
Phase III, randomized, placebo-controlled study of once-daily oral zibotentan (ZD4054) in patients with non-metastatic castration-resistant prostate cancer.
Trial report in Prostate cancer and prostatic diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Association of oral endothelin receptor antagonists with risks of cardiovascular events and mortality: meta-analysis of randomized controlled trials.European journal of clinical pharmacology · 2017Pooled it
- A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer.PloS one · 2015Pooled it
- Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy-Naive Metastatic Castrate-Resistant Prostate Cancer.The oncologist · 2019Trial
- Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer.The New England journal of medicine · 2018Trial
- Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800).Clinical genitourinary cancer · 2015Trial
- Article
- 20 years of taxane therapy in prostate cancer - the past, present and future.Nature reviews. Urology · 2026Review
- G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.MedComm · 2025Review
- Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.Cancer management and research · 2025Review
- Endothelin-1 Mediates Oxaliplatin Resistance via Activation of YAP Signaling in Colorectal Cancer.Oncology research · 2025Article
- Unveiling the Anti-cancer Potential of Oxadiazole Derivatives: A Comprehensive Exploration of Structure-Activity Relationships and Chemico-Biological Insights.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Endothelin and the tumor microenvironment: a finger in every pie.Clinical science (London, England : 1979) · 2024Review
- Efficacy and safety of zibotentan and dapagliflozin in patients with chronic kidney disease: study design and baseline characteristics of the ZENITH-CKD trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Anti-Anginal Efficacy of Zibotentan in the Coronary Slow-Flow Phenomenon.Journal of clinical medicine · 2024Article
- Rapid Assembly of Pyrrole-Ligated 1,3,4-Oxadiazoles and Excellent Antibacterial Activity of Iodophenol Substituents.Molecules (Basel, Switzerland) · 2023Article
- Ultrasound-assisted, low-solvent and acid/base-free synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols as potent antimicrobial and antioxidant agents.Molecular diversity · 2021Article
- Treatment and trials in non-metastatic castration-resistant prostate cancer.Nature reviews. Urology · 2021Review
- Article
- An efficient synthesis tetrazole and oxadiazole analogues of novel 2'-deoxy-C-nucleosides and their antitumor activity.Bioorganic & medicinal chemistry letters · 2020Article
- Endothelin-1-Mediated Drug Resistance inCancer research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundStandard treatment options are limited for the management of non-metastatic castration-resistant prostate cancer (CRPC). This study, part of the ENTHUSE (EndoTHelin A USE) phase III programme, evaluated the efficacy and safety of the oral specific endothelin (ET)A receptor antagonist zibotentan vs placebo in patients with non-metastatic CRPC (non-mCRPC).
methodsThis was a multicentre, randomized, double-blind, phase III study. Patients (n=1421) with non-mCRPC and biochemical progression (determined by rising serum PSA levels) were randomized to receive zibotentan 10 mg or placebo once daily. Based on the lack of efficacy signal in another ENTHUSE phase III study, an interim analysis was performed to determine whether the study was likely to achieve the co-primary objectives of improved overall survival (OS) and progression-free survival (PFS).
resultsCriteria for continuation of this study were not met. A total of 79 deaths and 293 progression events were recorded at final data cutoff. Zibotentan-treated patients did not significantly differ from placebo-treated patients for OS (hazard ratio (HR): 1.13; 95% confidence interval (CI): 0.73-1.76, P=0.589) or PFS (HR: 0.89; 95% CI: 0.71-1.12, P=0.330). The most commonly reported adverse events in zibotentan-treated patients were peripheral oedema (37.7%), headache (26.2%) and nasal congestion (24.9%); each occurred with >15% higher incidence than in the placebo group.
conclusionsThis trial was terminated early because of failure at interim analysis of the efficacy data to meet the defined criteria for continuation. Owing to the absence of demonstrable survival benefits in the ENTHUSE clinical studies, zibotentan is no longer under investigation as a potential treatment for prostate cancer.
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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.