Bortezornib in recurrent and/or refractory multiple myeloma - Initial clinical experience in patients with impaired renal function
Bortezornib in recurrent and/or refractory multiple myeloma - Initial clinical experience in patients with impaired renal function
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DOI：
10.1002/cncr.20888
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发表时间：
2005-03-15
期刊：
影响因子：
6.2
通讯作者：
Anderson, KC
中科院分区：
文献类型：
--
作者：
Jagannath, S;Barlogie, B;Anderson, KC
背景硼替佐米是一种有效的、可逆的蛋白酶体抑制剂，已被批准用于治疗复发性和/或难治性多发性骨髓瘤，但迄今为止尚未研究其在肾损害患者中的活性。方法.在复发性和/或难治性骨髓瘤患者中评估与基线肌酐清除率（CrCl）相关的缓解率、安全性和20 S蛋白酶体活性（n. = 256例患者），在2项11期试验中接受硼替佐米治疗。硼替佐米在21天周期的第1、4、8和11天静脉推注给药，剂量为1.0 mg/m2（n = 28例患者）和1.3 mg/m2（n = 228例患者）。结果在CrCl小于或等于30 mL/m2的10例患者中，7例患者完成了方案规定的8个周期的治疗; 4例患者接受了1.3 mg/m2硼替佐米剂量，3例患者接受了1.0 mg/m2硼替佐米剂量。使用欧洲血液和骨髓移植组标准，由独立委员会将缓解分配给10例患者中的3例（2例部分缓解和1例极轻微缓解），缓解率与总体治疗人群相似。CrCl > 80 mL/min（n = 105例患者）、51-80 mL/min（n = 99例患者）和小于或等于50 mL/min（n = 52例患者）的患者停药率和不良事件特征相似。肾功能似乎不影响给药后1小时蛋白酶体抑制或其恢复。结论.在有限数量的肾功能受损患者中的临床经验表明，硼替佐米在这一高危人群中提供了临床获益和可管理的毒性。癌症2005;103：1195-200。(C)2005年美国癌症协会。
BACKGROUND. Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date. METHODS. Response rates, safety, and 20S proteasome activity were assessed in relation to baseline creatinine clearance (CrCl) among patients with recurrent and/or refractory myeloma (n. = 256 patients) who were treated with bortezomib in 2 Phase 11 trials. Bortezomib was administered by intravenous bolus on Days 1, 4, 8, and 11 of a 21 -day cycle at 2 doses, 1.0 mg/m(2) (n = 28 patients) and 1.3 mg/m2 (n = 228 patients). RESULTS. Of 10 patients with CrCl less than or equal to 30 mL/mmute, 7 patients completed the protocol -specified 8 cycles of treatment; 4 patients received the 1.3 mg/m(2) bortezomib dose, and 3 patients received the 1.0 mg/m2 bortezomib dose. Using the European Group for Blood and Marrow Transplantation criteria, responses were assigned by an independent committee to 3 of the 10 patients (2 partial responses and 1 minimal response), a response rate similar to that of the overall treated population. Patients with CrCl > 80 mL/minute (n = 105 patients), 51-80 mL/ minute (n = 99 patients), and less than or equal to 50 mL/minute (n = 52 patients) had similar rates of discontinuation and similar adverse event profiles. Renal function did not appear to affect the 1-hour postdose proteasome inhibition or its recovery. CONCLUSIONS. Clinical experience in a limited number of patients with impaired renal function suggests that bortezomib provides clinical benefit with manageable toxicities in this high-risk population. Cancer 2005;103:1195-200. (C) 2005 American Cancer Society.