Pecherstorfer Martin, Rivkin Saul, Body Jean-Jacques, Diel Ingo, Bergström Bengt
Wilhelminenspital, Vienna, Austria.
Clin Drug Investig. 2006;26(6):315-22. doi: 10.2165/00044011-200626060-00002.
Despite their widespread use in metastatic bone disease, some bisphosphonate drugs are associated with adverse events (AEs), particularly renal toxicity, adding to treatment burdens and increasing healthcare costs. Ibandronic acid is a single-nitrogen bisphosphonate with high efficacy against bone events and metastatic bone pain, and a renal safety profile compar- able to that of placebo. In this study, the safety of ibandronic acid was examined over a period of 4 years.
During an initial 96-week period, breast cancer patients with bone metastases were randomised in double-blind fashion to placebo or ibandronic acid 6mg administered by intravenous infusion over 1-2 hours every 3-4 weeks as part of a previously reported phase III trial (MF 4265 study). All patients completing the phase III trial were offered open-label active treatment for a further 96 weeks (extension phase). A total of 62 patients received ibandronic acid 6mg in this extension phase and were classified according to their initial treatment (placebo/ibandronic acid 6mg [placebo/6mg] and ibandronic acid 6mg/ibandronic acid 6mg [6mg/6mg] groups). Safety was assessed by AE reports and clinical laboratory evaluations.
During the 4-year study, most patients experienced at least one AE, with malignancy progression being most commonly reported. However, fewer treatment-related AEs were reported in the extension phase (placebo/6mg: 6.3% [1/16]; 6mg/6mg: 13.0% [6/46]) than in the initial phase of the study (placebo: 56.3% [9/16]; 6mg: 67.4% [31/46]). Serious AEs were mainly due to malignancy progression. There were no clinically relevant renal AEs, and in both groups, serum creatinine levels were similar for up to 4 years.
This 96-week open-label safety extension of a phase III, placebo-controlled trial demonstrates that long-term use of intravenous ibandronic acid is well tolerated.
尽管双膦酸盐类药物在转移性骨病中广泛应用，但一些双膦酸盐类药物与不良事件（AE）相关，尤其是肾毒性，这增加了治疗负担并提高了医疗成本。伊班膦酸是一种单氮双膦酸盐，对骨事件和转移性骨痛具有高效，且肾安全性与安慰剂相当。在本研究中，对伊班膦酸4年期间的安全性进行了检查。
在最初的96周期间，骨转移乳腺癌患者以双盲方式随机分为安慰剂组或伊班膦酸6mg组，每3 - 4周静脉输注1 - 2小时，这是先前报道的一项III期试验（MF 4265研究）的一部分。所有完成III期试验的患者都接受了为期96周的开放标签活性治疗（延长期）。在这个延长期，共有62例患者接受伊班膦酸6mg治疗，并根据其初始治疗情况进行分类（安慰剂/伊班膦酸6mg [安慰剂/6mg]组和伊班膦酸6mg/伊班膦酸6mg [6mg/6mg]组）。通过不良事件报告和临床实验室评估来评估安全性。
在4年的研究期间，大多数患者至少经历了一次不良事件，最常报告的是恶性肿瘤进展。然而，与初始研究阶段相比，延长期报告的与治疗相关的不良事件较少（安慰剂/6mg组：6.3% [1/16]；6mg/6mg组：13.0% [6/46]）（安慰剂组：56.3% [9/16]；6mg组：67.4% [31/46]）。严重不良事件主要是由于恶性肿瘤进展。没有临床相关的肾不良事件，并且在两组中，长达4年血清肌酐水平相似。
这项III期安慰剂对照试验的96周开放标签安全性延长期表明，静脉注射伊班膦酸的长期使用耐受性良好。
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