Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Phase I/II Trial of Enzalutamide and Mifepristone, a Glucocorticoid Receptor Antagonist, for Metastatic Castration-Resistant Prostate Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis 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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Novel Therapeutic Strategies for Metastatic Prostate Cancer Care.European urology · 2025Pooled it
- Signaling Under Stress: Targeting the Glucocorticoid Receptor in Cancer.Cancer research · 2026Review
- High level expression of glucocorticoid receptor (GR) is linked to aggressive tumor features, early biochemical recurrence, and genetic instability in prostate cancer.Prostate cancer and prostatic diseases · 2026Article
- Androgen receptor reactivation in castration-resistant prostate cancer: mechanisms, epigenetic adaptation, and therapeutic vulnerabilities.Frontiers in oncology · 2026Review
- Characteristics and therapeutic resistance mechanisms of the prostate cancer immune microenvironment: a comprehensive analysis from bench to clinic.Frontiers in pharmacology · 2026Review
- The Pivotal Role of GR-CAR Pathway in Fetal Programming of Hepatic Cytochrome P450 3A Alteration in Adulthood.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genomic Crosstalk Between Nuclear Receptors in Hormone-dependent Cancers.Endocrinology · 2025Review
- Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.Journal of pharmaceutical analysis · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- BGATT-GR: accurate identification of glucocorticoid receptor antagonists based on data augmentation combined with BiGRU-attention.Scientific reports · 2025Article
- A TBX2-driven signaling switch from androgen receptor to glucocorticoid receptor confers therapeutic resistance in prostate cancer.Oncogene · 2025Article
- The future of androgen receptor targeting in prostate cancer: third-generation inhibitors and beyond.Therapeutic advances in medical oncology · 2025Review
- Inhibition of the Sterol Regulatory Element Binding Protein SREBF-1 Overcomes Docetaxel Resistance in Advanced Prostate Cancer.The American journal of pathology · 2024Article
- Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment.Expert review of anticancer therapy · 2024Review
- Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.Journal of experimental & clinical cancer research : CR · 2024Article
- A Phase I Trial of Enzalutamide Plus Selective Glucocorticoid Receptor Modulator Relacorilant in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells.Cellular and molecular life sciences : CMLS · 2024Article
- Phase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
purposeAlthough androgen deprivation therapy (ADT) and androgen receptor (AR) signaling inhibitors are effective in metastatic prostate cancer, resistance occurs in most patients. This phase I/II trial assessed the safety, pharmacokinetic impact, and efficacy of the glucocorticoid receptor (GR) antagonist mifepristone in combination with enzalutamide for castration-resistant prostate cancer (CRPC). PATIENTS AND
methodsOne hundred and six patients with CRPC were accrued. Phase I subjects were treated with enzalutamide monotherapy at 160 mg per day for 28 days to allow steady-state accumulation. Patients then entered the dose escalation combination portion of the study. In phase II, patients were randomized 1:1 to either receive enzalutamide alone or enzalutamide plus mifepristone. The primary endpoint was PSA progression-free survival (PFS), with radiographic PFS, and PSA response rate (RR) as key secondary endpoints. Circulating tumor cells were collected before randomization for exploratory translational biomarker studies.
resultsWe determined a 25% dose reduction in enzalutamide, when added to mifepristone, resulted in equivalent drug levels compared with full-dose enzalutamide and was well tolerated. However, the addition of mifepristone to enzalutamide following a 12-week enzalutamide lead-in did not delay time to PSA, radiographic or clinical PFS. The trial was terminated early due to futility.
conclusionsThis is the first prospective trial of dual AR-GR antagonism in CRPC. Enzalutamide combined with mifepristone was safe and well tolerated but did not meet its primary endpoint. The development of more specific GR antagonists combined with AR antagonists, potentially studied in an earlier disease state, should be explored.
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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.