ArticleTherapeutic advances in medical oncology2021
Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study.
Article in Therapeutic advances in medical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.Asian journal of andrology · 2023Pooled it
- Real-World Outcomes of Combination Therapy With Radium-223 and Enzalutamide Compared With Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer.Advances in urology · 2026Article
- Darolutamide in Combination with Radium-223 Exhibits Synergistic Antitumor Efficacy in LNCaP Prostate Cancer Models.International journal of molecular sciences · 2024Article
- Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis.Molecular oncology · 2024Article
- Treatment intensification with radium-223 plus enzalutamide in patients with metastatic castration-resistant prostate cancer.Frontiers in medicine · 2024Review
- Article
- Enhanced Antitumor Efficacy of Radium-223 and Enzalutamide in the Intratibial LNCaP Prostate Cancer Model.International journal of molecular sciences · 2023Article
- Optimized TherapeuticPharmaceuticals (Basel, Switzerland) · 2022Article
- Second generation androgen receptor antagonists and challenges in prostate cancer treatment.Cell death & disease · 2022Review
- Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRadium-223 and enzalutamide are approved agents for patients with metastatic castration-resistant prostate cancer (mCRPC). Combining radium-223 and enzalutamide to improve outcomes is of clinical interest due to their differing modes of action and non-overlapping toxicity profiles.
methodsThis phase II study enrolled patients with mCRPC and bone metastases. Patients received six cycles of radium-223 in combination with enzalutamide, followed by enzalutamide alone. The primary endpoint was safety for the combination; secondary endpoints included radiographic/clinical progression-free survival (PFS), PSA PFS, overall survival (OS), change in alkaline phosphatase, patient-reported pain outcomes and skeletal related events.
resultsForty-five patients received the combination treatment: 42 patients (93.3%) received all six cycles. Fourteen patients (31.1%) developed grade 3 or 4 toxicities, most commonly fatigue and neutropaenia. Fractures during the combination period occurred in four patients (8.9%). A further 13 patients (28.9%) developed fractures after completing combination treatment, giving a total of 17 patients (37.8%) who developed a fracture at any time on study. The median time to fracture was greater than 17.2 months [95% confidence interval (CI), 17.2-not estimable]. The median time to PSA progression was 18.1 months (95% CI, 12.68-22.60) and the median time to radiological/clinical progression was 28.0 months (95% CI, 22.54-not reached). At the primary analysis, 19 (42.2%) out of 45 patients had died with a median OS not reached (mean 34.8 months, standard error 1.4).
conclusionIn men with progressive mCRPC and bone metastases, the combination of radium-223 and enzalutamide was tolerable with the majority of patients completing the combination treatment. Bone fractures during the combination period were uncommon; however, we did identify a higher incidence of fractures occurring in patients after completing combination treatment. Bone health agents should be administered and bone health should be closely monitored following treatment with radium-223 and enzalutamide.
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