McKeage Kate, Plosker Greg L
Wolters Kluwer Health | Adis, Auckland, New Zealand.
Pharmacoeconomics. 2008;26(3):251-68. doi: 10.2165/00019053-200826030-00007.
Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with > or =1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid. In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159 200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness. In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.
唑来膦酸（择泰）是第三代含氮肠外双膦酸盐，适用于治疗实体瘤或多发性骨髓瘤引起的骨转移以及恶性肿瘤高钙血症（HCM）。在晚期乳腺癌或前列腺癌患者中，每3 - 4周静脉注射4毫克唑来膦酸，持续长达15个月，与安慰剂相比，显著降低了发生≥1次骨相关事件（SRE，不包括HCM）的患者比例。在晚期乳腺癌或多发性骨髓瘤患者中，每3 - 4周静脉注射4毫克唑来膦酸或90毫克帕米膦酸，持续长达25个月，SRE的发生率相似，但在乳腺癌患者中，与帕米膦酸相比，唑来膦酸将包括HCM在内的SRE风险额外降低了20%。在基于这些和/或其他试验的疗效和资源使用数据比较直接成本的模拟成本效用研究中，结果各不相同。在最近从英国国家医疗服务体系（NHS）角度进行的一项研究中，对晚期乳腺癌女性进行了为期10年的治疗期模拟，静脉注射唑来膦酸和口服伊班膦酸比不治疗更具优势。就每获得一个质量调整生命年（QALY）的增量成本而言，静脉注射唑来膦酸最具成本效益，其次是口服伊班膦酸、静脉注射帕米膦酸和静脉注射伊班膦酸。另外两项同样从NHS角度对晚期乳腺癌患者进行的模拟分析，评估了三种双膦酸盐疗法在接受激素治疗或静脉化疗患者中的成本效用。分析基于14.3个月（即预期生存期）进行模拟，假设与临床乳腺癌试验结果有显著差异。此外，唑来膦酸的疗效假设并非基于该药物的临床试验。这些分析结果表明，就每获得一个QALY的增量成本而言，口服伊班膦酸比静脉注射唑来膦酸和静脉注射帕米膦酸更具成本效益。在一项从第三方角度对晚期前列腺癌患者进行的为期15个月的全球模拟成本效益分析中，唑来膦酸与不治疗相比，每获得一个QALY的增量成本为159200美元（2000年价值），约为普遍接受的成本效益阈值的3倍。总之，最近的一项模拟经济分析表明，在晚期乳腺癌患者骨转移的管理中，静脉注射4毫克唑来膦酸相对于不治疗更具优势。相比之下，在晚期前列腺癌患者中，4毫克唑来膦酸与不治疗相比，每获得一个QALY的增量成本预计高于普遍接受的阈值。在晚期乳腺癌的情况下，与其他双膦酸盐相比，在一项研究中静脉注射唑来膦酸比口服或静脉注射伊班膦酸以及静脉注射帕米膦酸更具成本效益，但在另一项研究中比口服伊班膦酸成本效益更低。需要进一步比较静脉注射唑来膦酸与口服伊班膦酸的疗效和经济数据。同时，唑来膦酸似乎是治疗晚期乳腺癌患者以及可能不同类型晚期实体瘤患者骨转移最具成本效益的静脉双膦酸盐。
