Enzalutamide
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
Enzalutamide: Prostate leiomyoma
One-Sentence Summary
Enzalutamide is an androgen receptor inhibitor, originally used to treat prostate cancer. The TxGNN model predicts it may be effective for prostate leiomyoma. No clinical trials or publications directly support this top-ranked prediction, so it rests on model prediction only. The strongest evidence in the data compiled for this report (38 trials and 20 publications under “prostate neoplasm”) concerns the already-approved prostate cancer indication, not a new use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Prostate leiomyoma |
| TxGNN Prediction Score | 0.9957 |
| Evidence Level | L5 (model prediction only for the top-ranked indication) |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. From general pharmacology, enzalutamide is an androgen receptor (AR) inhibitor. It blocks ligand binding, nuclear translocation and DNA binding of the receptor, and this is the basis of its efficacy in prostate cancer.
The other top-ranked predictions are similar. Prostate leiomyoma, fibroma of prostate and benign prostate phyllodes tumor are rare prostatic tumors with no trials or publications. Brenner tumor is an ovarian tumor with no clear link to AR inhibition, and its score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Clinical Trial Evidence
The top-ranked prediction has no registered trials. The table below shows the most relevant trials from the closely related category “prostate neoplasm”. All of them study prostate cancer, the approved indication, so they are not evidence for a new use.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02446405 | Phase 3 | Active, not recruiting | 1125 | ENZAMET: enzalutamide vs conventional non-steroidal anti-androgen with first-line ADT in metastatic prostate cancer |
| NCT06551324 | Phase 3 | Active, not recruiting | 600 | MEVPRO-1: mevrometostat + enzalutamide vs enzalutamide or docetaxel in mCRPC after abiraterone |
| NCT06496581 | Phase 3 | Recruiting | 500 | Standard of care (including enzalutamide) ± 177Lu-PSMA-617 in poorly responding de novo mHSPC |
| NCT02987543 | Phase 3 | Completed | 387 | PROfound: olaparib vs enzalutamide or abiraterone in mCRPC with HRR gene mutations |
| NCT03834493 | Phase 3 | Terminated | 1244 | KEYNOTE-641: pembrolizumab + enzalutamide vs placebo + enzalutamide in mCRPC |
| NCT06136624 | Phase 3 | Recruiting | 1310 | OMAHA-003: opevesostat vs abiraterone or enzalutamide in mCRPC |
| NCT03641560 | Phase 4 | Completed | 52 | Safety and efficacy of enzalutamide in Indian patients with docetaxel-pretreated mCRPC |
| NCT06059118 | Phase 2 | Recruiting | 50 | APEX: DFMO and high-dose testosterone alternating with enzalutamide in mCRPC |
| NCT07512076 | Phase 2 | Not yet recruiting | 26 | Dose optimization of enzalutamide in elderly patients with advanced prostate cancer |
| NCT06228053 | Phase 2 | Recruiting | 53 | SX-682 (CXCR1/2 inhibitor) + enzalutamide in ARPI-resistant mCRPC |
Literature Evidence
The top-ranked prediction has no publications. The table below lists key publications from the related “prostate neoplasm” category, all about the approved prostate cancer indication.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31329516 | 2019 | RCT | J Clin Oncol | ARCHES: enzalutamide + ADT in metastatic hormone-sensitive prostate cancer |
| 29949494 | 2018 | RCT | N Engl J Med | PROSPER: enzalutamide in non-metastatic castration-resistant prostate cancer with rapidly rising PSA |
| 22894553 | 2012 | RCT | N Engl J Med | AFFIRM: increased survival with enzalutamide after chemotherapy |
| 41124201 | 2026 | RCT | N Engl J Med | EMBARK: improved survival with enzalutamide in biochemically recurrent prostate cancer |
| 42223064 | 2026 | RCT | N Engl J Med | Talazoparib + enzalutamide + ADT in metastatic prostate cancer |
| 39417629 | 2025 | Comparative | The Prostate | Real-world comparison of abiraterone, enzalutamide and apalutamide in mHSPC |
| 40439959 | 2025 | Comparative | Adv Ther | Overall survival with apalutamide vs enzalutamide in mCSPC |
| 32534790 | 2020 | Review | Trends Cancer | Treatment advances in advanced prostate cancer |
| 39275993 | 2024 | Review | Expert Rev Anticancer Ther | Current uses and resistance mechanisms of enzalutamide |
| 38859590 | 2024 | Preclinical | Adv Sci | Enzalutamide sensitizes CRPC cells to copper-mediated cell death |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02407329 | XTANDI | Not listed | Not listed |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (hormonal; androgen receptor inhibitor), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were recorded. Major-level interactions in the listed entries include bupropion, dolasetron and eliglustat. Many moderate-level interactions are also listed, for example famotidine, omeprazole, rabeprazole, hydrocortisone, dexamethasone, clarithromycin, aprepitant, loperamide, saxagliptin, linagliptin and empagliflozin.
- Other considerations noted in the analysis: seizure risk, fatigue and cardiovascular risk, plus CYP3A4/CYP2C8-related interactions. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (prostate leiomyoma) is supported by model score only, with no trials or publications. The strong Phase 3 evidence in the data concerns prostate cancer, the existing approved indication. It validates the model but is not a new repurposing opportunity.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Clarification of what “prostate cancer/brain cancer susceptibility” means clinically, and whether any real new-use hypothesis exists
- Dedicated preclinical or clinical evidence for any candidate beyond prostate cancer, such as benign prostate neoplasms
- Indication text for the Canadian licence (DIN 02407329) to confirm the approved indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.