Prescrire Int. 2006 Jun;15(83):98-100.
(1) When multiple myeloma relapses more than one year after initial treatment, the median survival time is only 12 to 15 months. (2) Bortezomib is a cytotoxic agent that inhibits the 26S proteasome, a complex involved in intracellular protein breakdown in mammals. Bortezomib was initially licensed for the treatment of myeloma after multiple treatment failure; its indications were subsequently modified to include second-line treatment. (3) Second-line bortezomib therapy has not been compared with haematopoietic stem cell grafting, a treatment with documented efficacy. (4) An unblinded comparative trial involving 54 patients requiring second-line treatment showed that bortezomib at a dose of 1.3 mg/m to the 2nd power (twice a week for two weeks, followed by a 10 day rest period) was significantly more effective than a dose of 1 mg/m to the 2nd power in terms of the median survival time (not determined in the 1.3 mg group, versus 26.7 months in the 1 mg group) and the median time to disease progression (11.7 versus 4.2 months). (5) Among 251 patients in whom first-line treatment had failed, bortezomib was significantly more effective than dexamethasone: the one-year survival rate was 80% versus 66% on dexamethasone, and the progression-free survival time was 6.2 months versus 3.5 months. (6) Adverse effects occurred in 30% to 60% of patients enrolled in clinical trials, and were severe in about 10% to 20% of patients. They mainly included fatigue, nausea and vomiting, diarrhoea, anaemia, thrombocytopenia, and peripheral neuropathy. Animal studies indicated a possible risk of cardiotoxicity, and cases of cardiac arrhythmias and conduction disorders were observed in clinical trials. (7) Bortezomib is metabolised by the cytochrome P450 isoenzyme CYP3A4, with a high risk of interactions. (8) The vials contain an excessive amount of this costly drug, creating a risk of inadvertent overdose and leading to unnecessary waste. (9) In practice, bortezomib is an alternative to steroid therapy for patients with multiple myeloma in whom first-line treatment has failed and who do not qualify for stem cell grafting. The choice of treatment must be discussed with the patient, after providing thorough information on the likely benefits and risks
(1) 多发性骨髓瘤在初始治疗一年多后复发时，中位生存时间仅为12至15个月。(2) 硼替佐米是一种细胞毒性药物，可抑制26S蛋白酶体，该复合体参与哺乳动物细胞内蛋白质的分解。硼替佐米最初在多次治疗失败后被批准用于治疗骨髓瘤；其适应证随后修改为包括二线治疗。(3) 二线硼替佐米治疗尚未与造血干细胞移植（一种有确切疗效的治疗方法）进行比较。(4) 一项涉及54例需要二线治疗患者的非盲对照试验表明，剂量为1.3mg/m²（每周两次，持续两周，随后休息10天）的硼替佐米在中位生存时间（1.3mg组未确定，1mg组为26.7个月）和疾病进展中位时间（11.7个月对4.2个月）方面显著优于1mg/m²的剂量。(5) 在251例一线治疗失败的患者中，硼替佐米显著比地塞米松更有效：一年生存率分别为80%和66%（地塞米松组），无进展生存时间分别为6.2个月和3.5个月。(6) 参加临床试验的患者中30%至60%出现不良反应，约10%至20%的患者不良反应严重。主要包括疲劳、恶心和呕吐、腹泻、贫血、血小板减少和周围神经病变。动物研究表明存在心脏毒性风险，临床试验中观察到心律失常和传导障碍病例。(7) 硼替佐米通过细胞色素P450同工酶CYP3A4代谢，有很高的相互作用风险。(8) 小瓶中含有过量这种昂贵药物，存在意外过量用药风险并导致不必要的浪费。(9) 在实际应用中，对于一线治疗失败且不符合干细胞移植条件的多发性骨髓瘤患者，硼替佐米是类固醇治疗的替代方案。必须在向患者充分告知可能的益处和风险后，与患者讨论治疗选择。
