Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Academic Unit of Clinical Oncology, Weston Park Hospital, CR-UK/YCR Sheffield Cancer Research Centre, Sheffield, UK.
Eur Urol. 2014 Feb;65(2):278-86. doi: 10.1016/j.eururo.2013.05.015. Epub 2013 May 13.
Advanced prostate cancer (PCa) is associated with skeletal 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.
晚期前列腺癌（PCa）与骨骼并发症相关，这既是由于骨转移的结果，也是由于由于去势治疗（ADT）导致的脆弱性相关骨折所致。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有关。
回顾晚期 PCa 中破骨细胞抑制剂的临床试验，讨论这些药物的不良事件概况，并讨论解决特定不良事件的策略。
在 PubMed 上搜索了有关晚期 PCa 中破骨细胞抑制剂的临床试验报告。由于唑来膦酸和地舒单抗在该疾病中最常用，因此这些试验是重点。回顾文献以确定解决与这些药物相关的不良事件的预防和管理的关键出版物。
讨论了试验的主要发现和不良事件。讨论了常见不良事件的预防和管理。
唑来膦酸可预防 ADT 引起的骨矿物质密度丢失，并延迟转移性去势抵抗性 PCa（mCRPC）中的骨骼相关事件。地舒单抗可降低 ADT 相关的脆性骨折发生率，延迟非转移性去势抵抗性疾病中的骨转移发生，并在 mCRPC 中预防骨骼并发症方面优于唑来膦酸。两种药物都与颌骨坏死和低钙血症相关的不良事件有关。地舒单抗更常见低钙血症。唑来膦酸需要根据肾功能不全调整剂量，在严重肾功能不全时禁忌使用，并且与肾功能恶化有关。适当的患者选择，密切关注口腔健康，补充钙和维生素 D，并监测实验室值是降低晚期 PCa 中破骨细胞抑制剂相关不良事件影响的有效策略。
