br Conclusion Our findings may help physicians in selecting

Conclusion Our findings may help physicians in selecting high-priority patients for bisphosphonate treatment. Zoledronic pteryxin is indicated for treating patients with MBD from any malignancy [1,35]; however, many patients do not receive treatment (especially in NSCLC and CRPC). Although it may not be cost-effective to treat all, assessing NTX or a similar osteolysis marker could help identify patients who both have a higher risk of SREs (which can be reduced with ZOL treatment) and who may also derive a worthwhile OS benefit from this relatively simple and well-tolerated intervention. Overall, our models suggest that patients with poor overall prognosis are more likely to derive OS benefits from ZOL, indicating that aggressive disease or impaired PS should not preclude ZOL treatment.
Funding
Conflict of Interest Statement
Research support
Acknowledgments We thank Shalini Murthy, PhD, ProEd Communications, Inc.®, for her editorial assistance with this manuscript. Medical editorial assistance was supported by Novartis Pharmaceuticals Corporation.
Background Despite the widespread use of bone-targeted therapies such as bisphosphonates (e.g. zoledronate, pamidronate, clodronate) or receptor activator of nuclear factor kappa-B ligand (RANKL) antibodies (i.e. denosumab) in patients with metastatic bone disease, many questions remain about their optimal use [1,2]. One question in particular pertains to identification of the optimal dosing frequency [3]. Bone-targeted agents are usually given every 3–4 weeks, a dosing interval that is based predominantly on their clinical development as an add-on treatment to standard anti-cancer therapies such as chemotherapy [4], along with data derived from the treatment of hypercalcemia from malignancy [5–7]. This “one size fits all” approach to the dosing intervals [8] is sub-optimal however, as it ignores the long half-life of these agents in bone [9] and the substantial variability in individual patient risk of skeletal related events (SREs) [10]. Given the modest magnitude of absolute benefit of bone-targeted agents on skeletal related event reductions, [2] chromosomes is important to investigate whether to not less frequent administration could affect the efficacy of these agents. This would not only result in reduced financial costs to both the patient and to the health care system, but would also likely reduce drug-associated toxicity. The latter is particularly important as toxicity of these agents has been shown to be related to both the potency and the cumulative dose of the bone-targeted agent [11]. To date, two trials have been presented assessing reduced frequencies of administration of these agents in metastatic breast cancer patients [12,13] and others are still on going [17]. Despite this, the results of the published trials would suggest that there is still a need for larger definitive studies. In addition, we are not aware of any similar studies planned for prostate cancer where again the benefits of bone-targeted agents in reducing SREs are likely even more modest than that seen in breast cancer patients. We are however aware of considerable variability in clinical practice, not only between cancer centers, but also within centers with respect to a number of questions around optimal use of bone-targeted agents, despite various clinical practice guidelines [3].
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Discussion There is considerable interest in optimizing the frequency of administration of bone-targeted agents as the current “one size fits all” approach is likely inefficient, expensive, and there is reason to believe that some patients may achieve equivalent benefit and improved safety with less frequent treatment administration. The results of the two published trials, assessing reduced frequencies of administration of these agents, would suggest there is still a need for larger definitive studies [12,13]. In addition, we are not aware of any similar studies planned for prostate cancer where again the benefits of bone-targeted agents in reducing SREs are likely even more modest than that seen in breast cancer patients.