Table 1.
FDA approved therapies for advanced prostate cancer*
| Group | Mechanism of action | Population studied (Trial name) | Intervention | Primary end point outcomes | Notable adverse effects |
|---|---|---|---|---|---|
| Docetaxel + Prednisone | Microtubule inhibitor | mCRPC (TAX327)91 | Arm 1: Docetaxel 75 mg/m2 IV q3 weeks + Prednisone 5 mg PO BID Arm 2: Mitoxantrone 12 mg/m2 IV q3 weeks + Prednisone 5 mg PO BID |
OS benefit: 2.4 months (18.9 versus 16.5 months) | Sensory neuropathy |
| Cabazitaxel + Prednisone | Semisynthetic taxane inhibiting microtubule depolymerization and cell division by binding to tubulin | mCRPC previously treated with a docetaxel-containing regimen (TROPIC)36 | Arm 1: Cabazitaxel 25 mg/m2 IV q3 weeks + Prednisone 5 mg PO BID Arm 2: Mitoxantrone 12 mg/m2 IV q3 weeks + Prednisone 5 mg PO BID |
OS benefit: 2.4 months (15.1 versus 12.7 months) | Neutropenia and diarrhea |
| Abiraterone + Prednisone | Selective and irreversible inhibitor of CYP17 | mCRPC previously treated with a docetaxel-containing regimen (COU-AA-301)23 | Arm 1: Abiraterone 1,000 mg PO daily + Prednisone 5 mg PO BID Arm 2: Placebo + Prednisone 5 mg PO BID |
OS benefit: 4.6 months (15.8 versus 11.2 months) | Mineralocorticoid excess (fluid retention, hypertension, hypokalemia) |
| mCRPC not pretreated with chemotherapy (COU-AA-302)25 | Arm 1: Abiraterone 1,000 mg PO daily + Prednisone 5 mg PO BID Arm 2: Placebo + Prednisone 5 mg PO BID |
rPFS benefit: 8.3 months (16.5 versus 8.2 months) OS increased (35.1 versus 30.1 months)** |
|||
| Enzalutamide | A pure AR signaling inhibitor with no agonistic properties. Also prevents the translocation of the AR from cytoplasm to nucleus, DNA binding, and co-activator mobilization | mCRPC previously treated with a docetaxel-containing regimen (AFFIRM)78 | Arm 1: Enzalutamide 160 mg PO daily Arm 2: Placebo |
OS benefit: 4.8 months (18.4 versus 13.6 months) | Fatigue, diarrhea, hot flashes, seizures |
| mCRPC not pretreated with chemotherapy *(PREVAIL)82 | Arm 1: Enzalutamide 160 mg PO daily Arm 2: Placebo |
OS benefit: 30% reduction in risk of death rPFS benefit: 81% reduction in risk of radiographic progression or death | |||
| Radium 223 | An alpha emitter, selectively targets bone metastases with alpha particles | mCRPC with symptomatic bone metastases and no known visceral metastatic disease. (ALSYMPCA)46 | Arm 1: One injection of radium-223 (at a dose of 50 kBq/kg) IV q4 weeks ×6 Arm 2: Placebo |
OS benefit: 3.6 months (14.9 versus 11.3 months) | Well tolerated with no clinical meaningful differences; pancytopenia |
| Sipuleucel-T | An autologous cellular immunotherapy designed to induce an immune response targeted against PAP, an antigen expressed in most prostate cancers | Asymptomatic or minimally symptomatic patients with mCRPC (IMPACT)34 | Arm 1: Sipuleucel-T q2 weeks ×3 infusions Arm 2: Placebo |
OS benefits: 4.1 months (25.8 versus 21.7 months) | Infusion-related pyrexia, myalgia, tremors |
Notes:
PREVAIL study data released, currently awaiting FDA approval
not statistically significant.
Abbreviations: AFFIRM, A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100; ALSYMPCA, Alpharadin in Symptomatic Prostate Cancer Patients; AR, androgen receptor; BID, twice daily; CYP17, microsomal enzyme cytochrome P450 isoform-17; FDA, US Food and Drug Administration; IMPACT, Immunotherapy for Prostate Adenocarcinoma Treatment;IV, intravenous; mCRPC, metastatic castration-resistant prostate cancer; OS, overall survival; PO, orally; rPFS, radiographic progression-free survival; PAP, prostatic acid phosphatase; PSA, prostate specific antigen; PFS, progression free survival; q3, every three.