Kaygusuz Isik, Toptas Tayfur, Aydin Fergun, Uzay Ant, Firatli-Tuglular Tulin, Bayik Mahmut
Division of Hematology, Marmara University Hospital, Istanbul, Turkey.
Hematology. 2011 Jul;16(4):200-8. doi: 10.1179/102453311X13025568941880.
Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of <60 and ≥60 ml/minute were similar. Although there was a tendency for shorter overall survival along lower estimated glomerular filtration rates, this difference did not reach a statistical significance. Overall and severe adverse events, and dose modification and treatment discontinuation rates were higher in patients with renal impairment. Patients with renal failure had more thrombocytopenia and diarrhea. While thrombocytopenia was mild to moderate and manageable, diarrhea, which led to serious adverse events, was more severe in patients with renal failure who received bortezomib as monotherapy. Bortezomib appears to be active; however, when used alone, it may cause more frequent and severe adverse events in patients with MM and renal failure.
肾衰竭是多发性骨髓瘤（MM）的常见表现。硼替佐米主要通过细胞色素P450同工酶代谢。它也有不依赖细胞色素的代谢途径，可通过胆汁和肾脏排泄。基于我们的观察，我们旨在探讨硼替佐米在56例MM患者中的疗效和毒性特征，其中24例患有中度至重度肾衰竭。肾功能正常和肾功能损害患者的总体缓解率、完全缓解率以及非常好的部分缓解率相当。估计肾小球滤过率<60和≥60 ml/分钟的患者的中位总生存期相似。尽管随着估计肾小球滤过率降低有总生存期缩短的趋势，但这种差异未达到统计学意义。肾功能损害患者的总体和严重不良事件、剂量调整和治疗中断率更高。肾衰竭患者有更多血小板减少和腹泻。虽然血小板减少为轻度至中度且可控制，但在接受硼替佐米单药治疗的肾衰竭患者中，导致严重不良事件的腹泻更为严重。硼替佐米似乎有活性；然而，单独使用时，它可能在MM和肾衰竭患者中引起更频繁和严重的不良事件。
