Table 4.
New agents for the treatment of metastatic castration-resistant prostate cancer
| Drug (trade name, manufacturer) | Mechanism | Toxicities | Target population | Outcomes from completed trials | Ongoing trials |
|---|---|---|---|---|---|
| Cabazitaxel (Jentava, Sanofi-Aventis) | Tubulin-binding taxane | Neutropenia, diarrhea, fatigue, nausea | mCRPC, docetaxel-refractory | (Phase III study) OS 15.1 vs 12.7 months for mitoxantrone (HR = 0.7; P < 0.001)20 | See “Critical appraisal” section above |
| MDV3100 (Medivation) | Androgen receptor antagonist | Fatigue, seizure in 3 patients | mCRPC, docetaxel-refractory or docetaxel-naïve | (Phase I/II study) PSA responses in 56% of men; radiographic responses in 22% of men; stable bone disease for 12 weeks in 56% of men32 | Phase III AFFIRM trial: MDV3100 vs. placebo in docetaxel-pretreated men with metastatic CRPC [NCT00974311] |
| Abiraterone (Cougar/Johnson and Johnson) | Androgen biosynthesis inhibitor that blocks CYP17 | Edema, hypokalemia, LFT elevation | mCRPC, docetaxel-refractory | (Phase III study) OS 14.8 vs 10.9 months for placebo (P < 0.0001). TTPP 10.2 vs 6.6 months (P < 0.0001). PSA response rate 38% vs 10% (P < 0.0001)33 | Phase III study of abiraterone vs. placebo in men with metastatic CRPC, chemotherapy-naïve [NCT00887198] |
| Custirsen (OGX-011, OncoGenex) | Apoptosis-inducing agent; targeting clusterin | Rash, fever, rigors, diarrhea, leucopenia, elevated creatinine | mCRPC, chemotherapy-naïve | (Phase II study) OS 23.8 months for custirsen and docetaxel vs 16.9 months for docetaxel alone (P = 0.06), but study not powered for OS34 | Phase III trial of docetaxel retreatment ± custirsen for men with docetaxel-refractory mCRPC [NCT01083615] |
| ProstVac-VF (Bavarian Nordic) | Poxviral-based immunotherapy | Injection-site reactions, fatigue, chills, nausea | mCRPC, chemotherapy-naïve | (Phase II study) Three-year OS 30% vs 17% in placebo group Median survival 25.1 vs 16.6 months (HR = 0.56, P = 0.006)35, but study was not powered for OS | Randomized Phase II trial of docetaxel ± ProstVac-VF in men with metastatic CRPC, chemo-naïve [NCT01145508] |
| Sipuleucel T (Provenge, Dendreon) | Autologous APC-based cellular immunotherapy | Chills, fever, headaches | mCRPC, chemotherapy-naïve (and some chemotherapy-pretreated) | (Phase III IMPACT trial) Median OS 25.8 vs 21.7 months for placebo (P = 0.03); 3-year OS 31.7% vs 23%27 | Phase III study in newly-diagnosed hormone-naïve patients with mCRPC, examining hormone therapy ± sipuleucel-T [currently being planned] |
Abbreviations: OS, overall survival; TTPP, time to PSA progression; PSA, prostate-specific antigen; PFS, progression free survival; mCRPC, metastatic castration-resistant prostate cancer; HR, hazard ratio; APC, antigen-presenting cell; LFT, liver function tests.