Toxicities following treatment with bisphosphonates and receptor activator of nuclear factor-κB ligand inhibitors in patients with advanced prostate cancer.
Toxicities following treatment with bisphosphonates and receptor activator of nuclear factor-κB ligand inhibitors in patients with advanced prostate cancer.
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DOI：
10.1016/j.eururo.2013.05.015
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发表时间：
2014-02
期刊：
影响因子：
23.4
通讯作者：
Galsky MD
中科院分区：
文献类型：
--
作者：
Gartrell BA;Coleman RE;Fizazi K;Miller K;Saad F;Sternberg CN;Galsky MD
晚期前列腺癌（PCa）与骨骼并发症有关，这既有骨转移的结果，也有与雄激素剥夺治疗（ADT）引起的脆性相关的骨折。破骨细胞抑制剂通常用于减少骨骼并发症，但与许多潜在的不良事件相关。回顾破骨细胞抑制剂治疗晚期前列腺癌的临床试验，讨论这些药物的不良事件特征，并讨论解决特定不良事件的策略。检索PubMed中有关破骨细胞抑制剂治疗晚期PCa的临床试验报告。由于唑来膦酸和狄诺塞单抗最常用于这种疾病，因此这些试验是重点。对文献进行了回顾，以确定涉及预防和管理与这些药物相关的不良事件的关键出版物。主要结果的试验和不良事件进行了讨论。常见不良事件的预防和管理。唑来膦酸可预防ADT相关的骨密度丢失，并延迟转移性去势抵抗性PCa（mCRPC）患者的泌尿系统相关事件。Denosumab可降低ADT相关脆性骨折的发生率，延迟非转移性去势抵抗性疾病的骨转移发生，在预防mCRPC骨骼并发症方面优于唑来膦酸上级。与两种药物相关的不良事件包括颌骨骨坏死和低钙血症。低钙血症在地舒单抗治疗中更常见。唑来膦酸因肾功能不全需要调整剂量，禁忌用于重度肾功能不全，并与肾功能恶化相关。适当的患者选择，密切关注牙齿健康，补充钙和维生素D，并监测实验室值是有效的策略，以尽量减少与破骨细胞抑制剂相关的不良事件在晚期PCa的影响。
Advanced prostate cancer(PCa) is associated withskeletal complications, both as a result of bone metastases and because of fractures associated with fragility due to androgen-deprivation therapy (ADT). Osteoclast inhibitors are commonly used to reduce skeletal complications but are associated with a number of potential adverse events. To review clinical trials of osteoclast inhibitors in advanced PCa, to discuss the adverse event profile of these agents, and to discuss strategies to address specific adverse events. PubMed was searched for reports of clinical trials of osteoclast inhibitors in advanced PCa. As zoledronic acid and denosumab are used most commonly in this disease, these trials were the focus. The literature was reviewed to identify key publications addressing the prevention and management of adverse events associated with these drugs. The major findings of the trials and the adverse events are discussed. Prevention and management of common adverse events are addressed. Zoledronic acid prevents loss of bone mineral density associated with ADT and delays skeletal-related events in metastatic castration-resistant PCa (mCRPC). Denosumab reduces the incidence of fragility fractures associated with ADT, delays the onset of bone metastases in nonmetastatic castration-resistant disease, and is superior to zoledronic acid in the prevention of skeletal complications in mCRPC. Adverse events associated with both agents include osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab. Zoledronic acid requires dose modifications for renal insufficiency, is contraindicated in severe renal insufficiency, and has been associated with deterioration of renal function. Appropriate patient selection with close attention to dental health, supplementation with calcium and vitamin D, and monitoring of laboratory values are effective strategies to minimize the impact of adverse events associated with osteoclast inhibitors in advanced PCa.