Castrate-resistant prostate cancer: postdocetaxel management.
OBJECTIVE
Prior to 2010, docetaxel was the only treatment shown to prolong survival in metastatic castrate-resistant prostate cancer (CRPC). In the past 3 years, several therapeutic agents have demonstrated survival improvements for CRPC after the receipt of prior docetaxel, leading to multiple approvals by the US Food and Drug Administration.


RESULTS
The development of these novel agents, each with a distinct mechanism of action, is the fruition of sedulous preclinical research and well designed clinical trials. Cabazitaxel, a next generation taxane, was the first Food and Drug Administration-approved drug for the postdocetaxel setting. The recognition of sustained androgen dependence of CRPC has led to the identification of more potent and selective inhibitors of androgen synthesis and androgen-receptor signaling, such as abiraterone and enzalutamide, respectively. Radium-223, an α-emitting radionuclide still under regulatory review, recently showed a significant survival benefit for CRPC. Finally, sipuleucel-T, a form of immunotherapy, may benefit a subset of patients in the postdocetaxel setting.


CONCLUSIONS
Post-docetaxel management of CRPC has undergone a dramatic yet welcome paradigm change in the past 3 years. With multiple life-prolonging agents available, it now becomes imperative to coordinate how and when these new therapies should be used and sequenced to achieve optimal patient outcomes.
Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, WA 98109, USA.
Song
S
Zhao
Evan Y
EY
Yu
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D007167:Immunotherapy / Q000379:methods; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel