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 441234T AU 421756287212441234M Aapro and F SaadTherapeutic Advances in Urology 2012Therapeutic Advances in Urology 4 (2) 86 http://tau.sagepub.com tumor-stimulating growth factors from the bone [Mundy, 2002]. The resulting vicious cycle of cancer growth and bone destruction can lead to skeletal-related events (SREs), including pathologic fractures, spinal cord compression, the need for palliative radiotherapy, surgery to bone, cementoplasty, and hypercalcemia of malignancy [Coleman, 2001]. Without bone-directed treatment, the majority of patients with advanced PC will experience an SRE during the course of their disease [Saad et al. 2004]. Moreover, in retrospective analyses of a 21-month, randomized, phase III, placebo-controlled trial in patients with bone metastases from solid tumors (excluding breast or prostate cancer) [Rosen et al. 2004], approximately 75% of patients in the RCC subset who did not receive bisphosphonate (BP) therapy developed an SRE [Saad and Lipton, 2005].Even before the development of bone metastases, bone health may be compromised in patients with GU cancers because of age-related osteoporosis and the detrimental effects of anticancer therapies on bone mineral density (BMD). This is most evident in the PC setting, wherein surgical or hormonal castration (androgen-deprivation therapy [ADT]) to lower testosterone levels is common in patients who have high-risk disease, or whose pros...

Evaluation of safety and analgesic consumption in patients with advanced cancer treated with zoledronic acid

“…Zoledronic acid reduces all types of skeletal related events compared to placebo in cancers, metastatic to bone, by 36% 7,8. Prostate cancer patients are at an even greater risk of skeletal related events than other cancer patients with bone metastases due to hormonal treatment induced secondary osteoporosis.…”

“…However, literature reveals that continuation treatment nevertheless maintain its efficacy, preventing subsequent skeletal related events 6,7. Furthermore, the pre-clinical studies demonstrated bisphosphonates’ inhibiting effect on cancer development 8. Some showed even increased survival in patients on regular treatment with zoledronic acid compared to the placebo group 7…”

Systemische Tumortherapie bei älteren Patienten

“…Eine langfristige Androgendeprivation kann sekundär zu Osteoporose füh-ren und eine altersbedingte physiologische Abnahme des Mineralstoffgehalts der Knochen mit erhöhter Anfälligkeit für Knochenbrüche verstärken. Es sollte daher bei der Einleitung einer androgendeprivierenden Therapie der Einsatz knochenprotektiver Maßnahmen evaluiert werden, ein routinemäßiger Einsatz wird allerdings nicht empfohlen [32]. Ein entsprechendes Risikoprofil kann eine Knochendichtemessung vor Einleitung der Therapie sinnvoll erscheinen lassen.…”

Management of Advanced Prostate Cancer in Senior Adults: The New Landscape

“…It is recommended that all men receiving ADT should therefore receive calcium and vitamin D supplementation, and baseline bone mineral density should be determined. Bisphosphonates or denosumab may be used if there is a documented risk for fracture or castrateresistant prostate cancer (CRPC) with skeletal metastases [12,13,24,25]. There is also a risk of metabolic side effects, diabetes, and fatal cardiac events [26 -29].…”

“…Approximately three-quarters of patients with prostate cancer develop bone metastases, often at the first diagnosis of metastatic disease [52]. Until recently, bisphosphonates were the only bone-targeted supportive treatment available [24,53].…”