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Traitements inhibiteurs de la résorption osseuse en situation métastatique : bilan actuel et perspectives

Inhibitors of bone resorption for the treatment of bone metastases: Current status and perspectives

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Oncologie

Résumé

L’usage principal des inhibiteurs de la résorption osseuse, les bisphosphonates et le dénosumab, réside actuellement dans la prévention des complications des métastases osseuses. Des perfusions mensuelles d’acide zolédronique, le bisphosphonate le plus puissant, réduisent les complications de l’ostéolyse tumorale d’environ 40 %. Des études récentes de phase III ont démontré la supériorité du dénosumab par rapport à l’acide zolédronique pour réduire la morbidité osseuse en cas de cancer mammaire ou prostatique généralisé au niveau osseux, tandis que le dénosumab s’est révélé non inférieur à l’acide zolédronique dans l’étude portant sur les autres tumeurs solides et le myélome multiple. La toxicité globale des deux composés était similaire. Il est recommandé de débuter un inhibiteur de la résorption osseuse dès le diagnostic de métastases osseuses, en tout cas dans le cancer mammaire, mais le traitement avec ces inhibiteurs puissants de la résorption osseuse devrait être progressivement individualisé afin de mieux définir les indications de traitements espacés et de réduire la fréquence des effets secondaires. Enfin, l’acide zolédronique mais aussi le clodronate peuvent réduire le risque d’apparition de métastases osseuses et prolonger la survie chez les patientes ménopausées en situation adjuvante, mais cette possible indication des inhibiteurs de la résorption osseuse n’est pas encore reconnue.

Abstract

The current main use of inhibitors of bone resorption, bisphosphonates and denosumab, is the prevention of the complications of bone metastases. Monthly infusions of zoledronic acid, the most potent bisphosphonate, decrease the complication rate of tumor-induced osteolysis by about 40%. Recent controlled double-blind phase III trials have demonstrated the superiority of denosumab against zoledronic acid to decrease skeletal morbidity in patients with bone metastases from breast or prostate cancer, and its noninferiority in a third trial including patients with other solid tumors or myeloma. The overall toxicity was similar between both compounds. It is recommended to start an inhibitor of bone resorption as soon as bone metastases are diagnosed, at least in patients with breast cancer. However, the optimal duration of therapy is unknown and we lack validated criteria to better individualize therapy and to define the place of intermittent treatments or of larger intervals between infusions. Lastly, recent studies indicate that zoledronic acid, but also clodronate, are able to reduce the risk of bone metastases and to prolong survival, at least in postmenopausal patients with breast cancer after surgery. This use of inhibitors of bone resorption in the adjuvant setting is not admitted yet although clinical practice is likely to change in the near future.

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  1. Service de médecine, CHU Brugmann, université Libre de Bruxelles (ULB), 4, place van-Gehuchten, B-1020, Bruxelles, Belgique

    J.-J. Body

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Body, JJ. Traitements inhibiteurs de la résorption osseuse en situation métastatique : bilan actuel et perspectives. Oncologie 17, 117–126 (2015). https://doi.org/10.1007/s10269-015-2494-3

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