Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

Table 1

Characteristics of selected FDA-approved bone targeting agents in mCRPC.

	Zoledronic acid	Denosumab	Sr-89	Sm 153	Ra 223
Class	Bisphosphonate	Monoclonal antibody against RANK-L	Pure Beta-emitter radiopharmaceutical	Beta and Gamma-emitter radiopharmaceutical	Alpha-emitter
Major side effects	Flu-like symptoms, hypocalcemia, osteonecrosis of the jaw	Hypocalcemia, osteonecrosis of the jaw	myelosuppression	myelosuppression	Nausea, vomiting, diarrhea.
Half-life (days)	6	25.4	50	1.9	11.4
Landmark randomized trial	Saad et al., 2002, 2004 [5, 6]	Fizzazi et al., 2011 [16]	Lewington et al., 1991 [17]	Serafini et al., 1998 [18]; Sartor et al., 2004, 2007 [19, 20]	Parker et al., 2012 [21]
Arms	Zoledronic acid versus placebo (𝑛=643)	Denosumab versus zoledronic acid (𝑛=1940)	Sr-89 versus placebo (𝑛=32)	Sm 153 versus placebo (𝑛=118)	Ra 223 versus placebo (𝑛=922)
Endpoint	Significant decrease and delay in SREs and bone pain	Significant delay in SREs	Significant decrease in bone pain	Significant decrease in bone pain	Significant increase in OS, PSA drop
Status	FDA approved 2002	FDA approved 2010	FDA approved; 1993	FDA approved 1997	FDA approved 2013
Administration	Intravenous	Subcutaneous	Intravenous	Intravenous	Intravenous