Bortezomib (Velcade) is Not Effective for Prostate Cancer
Bortezomib should not be used for treating prostate cancer, as clinical trials have demonstrated no meaningful efficacy and it is not included in any established treatment guidelines for this disease. 1
Evidence from Clinical Trials
Phase II Trial Results
- A phase II trial combining weekly docetaxel with bortezomib in hormone-refractory prostate cancer showed no improvement over docetaxel alone, with only 25% of patients achieving >50% PSA reduction (95% CI: 15%-38%) 2
- Median progression-free survival was only 4.1 months and overall survival 13.8 months, which is not superior to standard docetaxel monotherapy 2
- The investigators concluded that "bortezomib has minimal activity in patients with HRPC and is unlikely to make any impact on treatment efficacy" 2
Preclinical Concerns
- While bortezomib showed some activity in laboratory models 3, 4, a neoadjuvant clinical trial revealed an unexpected increase in tumor proliferation in treated prostate tissues 5
- Bortezomib paradoxically increased levels of SRC-3 and phosphorylated Akt, both pro-survival pathways, suggesting potential mechanisms of resistance 5
- In vitro studies suggest bortezomib would require combination with Akt inhibitors to overcome this resistance mechanism 5
Guideline-Recommended Treatments Instead
For Metastatic Hormone-Sensitive Prostate Cancer
- Continuous androgen deprivation therapy (ADT) is the foundation of treatment 1, 6
- For fit patients with de novo metastatic disease, especially those with multiple bone metastases or visceral metastases, ADT + docetaxel + abiraterone + prednisone is recommended 1
- Alternative regimens include ADT + docetaxel + darolutamide or ADT + novel hormone agent (abiraterone, apalutamide, or enzalutamide) 1
For Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- Docetaxel chemotherapy remains appropriate for symptomatic patients with good performance status 1
- After docetaxel failure, options include cabazitaxel 1
- For patients with BRCA1/BRCA2 alterations, olaparib improves overall survival (HR 0.69, medians: 19.1 vs 14.7 months) 1
- Lutetium-177 PSMA-617 combined with standard care improves both radiographic PFS and OS in pretreated patients 1
Why Bortezomib is Not Recommended
Absence from Guidelines
- Bortezomib is not mentioned in any ESMO, NCCN, or other major prostate cancer treatment guidelines 1, 7
- All guidelines focus on androgen deprivation, taxane chemotherapy, novel hormone agents, and PARP inhibitors—bortezomib is conspicuously absent 1
Approved Indication
- Bortezomib is FDA-approved and guideline-recommended only for multiple myeloma, not prostate cancer 1
- The drug's mechanism (proteasome inhibition) has proven effective in hematologic malignancies but failed to translate to prostate cancer efficacy 2, 3
Critical Pitfall to Avoid
- Do not confuse preclinical activity or phase I safety data with clinical efficacy—bortezomib showed biological effects in prostate tissue but no meaningful clinical benefit 3, 5
- The increase in tumor proliferation and activation of survival pathways (Akt) observed with bortezomib treatment suggests it may actually be counterproductive as monotherapy 5