Docetaxel-based combination therapy for castration-resistant prostate cancer.
BACKGROUND
Once castration resistance is documented and secondary hormone therapy is ineffective, standard treatment of metastatic prostate cancer is docetaxel, with bisphosphonates and radiopharmaceuticals administered to treat bone symptoms. To improve outcomes, numerous studies have evaluated docetaxel in combination with other agents. Here, results for docetaxel-based combination therapy in castration-resistant prostate cancer (CRPC) are reviewed.


METHODS
Relevant studies were identified in databases of published literature, clinical trials, and conference abstracts using the search terms docetaxel and prostate, with additional searches carried out for identified agents.


RESULTS
Numerous classes of agents have been combined with docetaxel in phase II studies in CRPC, including tyrosine kinase inhibitors, antiangiogenic agents, bone-targeted agents, BCL-2 inhibitors, chemotherapies, immunologic agents, and vitamin D analogs. In several cases, promising rates of prostate-specific antigen response, tumor response, and survival have been reported. However, some combinations have caused increased toxicity. Phase III trials with docetaxel plus GVAX or DN-101 were terminated because of lower survival; phase III trials with docetaxel plus bevacizumab, aflibercept, dasatinib, zibotentan, atrasentan, or lenalidomide are ongoing.


CONCLUSIONS
Docetaxel-based doublet therapy remains an active investigational strategy in CRPC. Further phase III data are awaited to determine whether survival can be extended compared with docetaxel alone.
Galsky
M D
MD
Comprehensive Cancer Centers of Nevada, Las Vegas, NV; US Oncology Research, Houston, TX, USA. Electronic address: Matthew.Galsky@usoncology.com.
Vogelzang
N J
NJ
Comprehensive Cancer Centers of Nevada, Las Vegas, NV; US Oncology Research, Houston, TX, USA.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002369:Castration; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000601:surgery; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage
D043823:Taxoids; D000077143:Docetaxel