Long-term benefits versus side-effects from bone-targeted therapies for cancer patients

Jacobs, Carmel; Ng, Terry L.; Ong, Michael; Clemons, Mark

doi:10.1097/spc.0000000000000084

Cited by 9 publications

(6 citation statements)

References 75 publications

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“…As for morphine, there are, however, some safety concerns about prolonged use of bisphosphonates. Indeed, patients taking zoledronate are at risk of developing osteonecrosis of the jaws, cardiovascular toxicity and impairment of renal function 29 .…”

Section: Introductionmentioning

confidence: 99%

Dichotomic effects of clinically used drugs on tumor growth, bone remodeling and pain management

Barrière

Midavaine

Doré-Savard

et al. 2019

Sci Rep

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Improvements in the survival of breast cancer patients have led to the emergence of bone health and pain management as key aspects of patient’s quality of life. Here, we used a female rat MRMT-1 model of breast cancer-induced bone pain to compare the effects of three drugs used clinically morphine, nabilone and zoledronate on tumor progression, bone remodeling and pain relief. We found that chronic morphine reduced the mechanical hypersensitivity induced by the proliferation of the luminal B aggressive breast cancer cells in the tumor-bearing femur and prevented spinal neuronal and astrocyte activation. Using MTT cell viability assay and MRI coupled to 18FDG PET imaging followed by ex vivo 3D µCT, we further demonstrated that morphine did not directly exert tumor growth promoting or inhibiting effects on MRMT-1 cancer cells but induced detrimental effects on bone healing by disturbing the balance between bone formation and breakdown. In sharp contrast, both the FDA-approved bisphosphonate zoledronate and the synthetic cannabinoid nabilone prescribed as antiemetics to patients receiving chemotherapy were effective in limiting the osteolytic bone destruction, thus preserving the bone architecture. The protective effect of nabilone on bone metabolism was further accompanied by a direct inhibition of tumor growth. As opposed to zoledronate, nabilone was however not able to manage bone tumor-induced pain and reactive gliosis. Altogether, our results revealed that morphine, nabilone and zoledronate exert disparate effects on tumor growth, bone metabolism and pain control. These findings also support the use of nabilone as an adjuvant therapy for bone metastases.

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Section: Introductionmentioning

confidence: 99%

Dichotomic effects of clinically used drugs on tumor growth, bone remodeling and pain management

Barrière

Midavaine

Doré-Savard

et al. 2019

Sci Rep

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“…Einige Nebenwirkungen beruhen auf der potenten antiresorptiven Wirkung beider Medikamente und sind beiden Substanzgruppen gemeinsam. Dazu zählen die Hypokalzämie, die Osteonekrose des Kieferknochens und die atypischen subtrochanterischen Femurfrakturen [14].…”

Section: Bisphosphonate Und Denosumabunclassified

“…Zu bedenken sind auch Kontraindikationen, wie ein primärer Hyperparathyreoidismus oder Nierensteine. Aufgrund der höheren PotenzvonDenosumabgegenüberBisphos-phonaten scheint auch eine Hypokalzämie unter diesem Wirkstoff häufiger zu sein [14]. …”

Section: Hypokalzämieunclassified

Knochenmetastasen

2016

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The occurrence of bone metastases, in particular secondary to breast and prostate cancer, represents a complex medical condition that is debilitating for affected patients. In order to provide an efficient and personalized therapy, an interdisciplinary treatment approach is mandatory; therefore, systemic pharmacological therapy represents a core element of the overall treatment concept. In terms of pathophysiology, the cancer cells cause a massive disturbance of the local bone microenvironment, which as a rule leads to activation of bone resorbing osteoclasts. In addition to bisphosphonates, which can be considered classical antiresorptive agents, the monoclonal receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab has been in use in clinical practice since 2011. The alpha-emitting radioisotope Alpharadin was also recently approved for the treatment of metastatic prostate cancer. This article provides a summary of the most recent knowledge on the pathogenesis of how cancer cells alter the bone microenvironment as well as a review of established and future systemic treatment options.

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“…Based on several randomized controlled trials, bone-modifying agents (BMAs) such as bisphosphonates, including pamidronate and zoledronate, and Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) inhibitors such as denosumab, reduce the incidence of SREs and delay the time to their onset [9] , [10] , [11] , [12] , [13] , [14] , [15] . These agents have therefore become an established international standard of care in the treatment of breast cancer and castration-resistant prostate cancer (CRPC) patients with bone metastases [16] , [17] , [18] , [19] , [20] , [21] . Despite their widespread use, many questions still exist around the optimal use of BMA, especially after 2 years of administration, where very little prospective data exists.…”

Section: Introductionmentioning

confidence: 99%

Real-world practice patterns and attitudes towards de-escalation of bone-modifying agents in patients with bone metastases from breast and prostate cancer: A physician survey

Alzahrani

Clemons

Vandermeer

et al. 2021

Journal of Bone Oncology

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Long-term benefits versus side-effects from bone-targeted therapies for cancer patients

Abstract: This article explores strategies to maximize the clinical benefit of such therapy while minimizing associated risks.

Cited by 9 publications

References 75 publications

Dichotomic effects of clinically used drugs on tumor growth, bone remodeling and pain management

Dichotomic effects of clinically used drugs on tumor growth, bone remodeling and pain management

Knochenmetastasen

Real-world practice patterns and attitudes towards de-escalation of bone-modifying agents in patients with bone metastases from breast and prostate cancer: A physician survey

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