Bone-modifying agents in the treatment of bone metastases in patients with advanced genitourinary malignancies: a focus on zoledronic acid

Abstract

Many patients with advanced genitourinary malignancies develop bone metastases, which can lead to potentially debilitating skeletal complications. Moreover, age-related bone loss and cancer treatments such as hormonal therapy for prostate cancer can weaken bone, placing patients at risk for osteoporotic fractures in addition to skeletal-related events (SREs) from bone metastases. Zoledronic acid, a bisphosphonate, is approved worldwide to reduce the risk of SREs in patients with bone metastases from solid tumors or bone lesions from multiple myeloma. Zoledronic acid, although underutilized in genitourinary malignancies, has long been the mainstay of treatment in patients with bone metastases, and can also help preserve bone during anticancer therapy. Recently, denosumab, a monoclonal antibody directed against the receptor activator of nuclear factor kappa-B ligand, was approved in the United States and the European Union for reducing the risk of SREs in patients with bone metastases from solid tumors. Denosumab (at a lower dose) is also approved in the European Union and the United States to treat androgen deprivation-induced bone loss in men with prostate cancer. In addition, preclinical rationale and emerging clinical data suggest that bone-modifying agents may be able to delay disease progression in genitourinary cancers, just as newly developed anticancer treatments have produced reductions in SREs, possibly by indirect effects on the disease course. This review article summarizes current data and ongoing studies to preserve bone health in patients with advanced genitourinary cancers.

Keywords: bisphosphonate; bone metastases; genitourinary cancer; prostate cancer; zoledronic acid.

Figure 1.

Zoledronic acid (4 mg every 3–4 weeks) delayed the first on-study skeletal-related event (SRE) (a) and pathologic fracture (b) compared with placebo in patients with bone metastases from castration-resistant prostate cancer. Reproduced with permission from Saad and Lipton [2005]. © 2005 John Wiley and Sons.

Figure 2.

Zoledronic acid improved skeletal-related event (SRE)-free survival (a) and overall survival (b) compared with placebo in patients with bone metastases from bladder cancer. Reproduced with permission from Zaghloul et al. [2010].

Figure 3.

Most frequently reported adverse events in the phase III placebo-controlled trial of zoledronic acid (4 mg every 3–4 weeks) in men with bone metastases from castration-resistant prostate cancer. Adapted with permission from Parker [2005]. © 2005 John Wiley and Sons.

Figure 4.

Persistency with zoledronic acid (ZOL) treatment was associated with a lower monthly rate of skeletal-related events in patients with bone metastases from solid tumors. Reproduced with permission from Hatoum et al. [2008]. © 2008 American Cancer Society.