A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma.
A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma.
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DOI：
10.1111/bjh.13900
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发表时间：
2016-03
影响因子：
6.5
通讯作者：
Iida S
中科院分区：
文献类型：
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作者：
Watanabe T;Tobinai K;Matsumoto M;Suzuki K;Sunami K;Ishida T;Ando K;Chou T;Ozaki S;Taniwaki M;Uike N;Shibayama H;Hatake K;Izutsu K;Ishikawa T;Shumiya Y;Kashihara T;Iida S
我们在日本复发性/难治性多发性骨髓瘤患者中开展了一项卡非佐米单药治疗的I/II期研究。在I期研究中检查了卡非佐米的安全性、药代动力学和药效学。II期研究的主要终点是总缓解率（ORR）。卡非佐米以每周两次、连续一天的给药方案给药。在I期，按照该方案给予15或20 mg/m2剂量，或在周期1第1天和第2天给予20 mg/m2剂量，然后在20/27 mg/m2队列中给予27 mg/m2剂量。患者既往接受过中位5种治疗，包括硼替佐米和免疫调节剂。剂量水平未达到最大耐受剂量。最常见的不良事件是血液学。值得注意的是，卡非佐米在50例患者中的10例中诱发了新发高血压（n = 4）或加重了既往高血压（n = 6）。8例既往发生周围神经病变（PN）的患者中有4例在使用卡非佐米后复发，但未发生新的PN病例。20/27 mg/m2 40例患者队列的ORR与关键美国研究相似。在接受过大量预治疗的日本患者中，该剂量有效且可耐受;但是，进一步使用卡非佐米可能需要仔细控制高血压。
We conducted a phase 1/2 study of single‐agent carfilzomib in Japanese patients with relapsed/refractory multiple myeloma. Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (ORR). Carfilzomib was administered in a twice‐weekly, consecutive‐day dosing schedule. In Phase 1, doses of 15 or 20 mg/m2 were administered on this schedule or 20 mg/m2 on Days 1 and 2 of Cycle 1 and then 27 mg/m2 in the 20/27 mg/m2 cohort. Patients had a median of five prior therapies, including bortezomib and an immunomodulatory agent. The dose level did not reach the maximum tolerated dose. The most common adverse events were haematological. Notably, carfilzomib either induced new hypertension (n = 4) or aggravated previously existing hypertension (n = 6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (PN) experienced a recurrence with carfilzomib use, but no new cases of PN occurred. The ORR of the 20/27 mg/m2 40 patient cohort was similar to that in the pivotal US study. The dose was efficacious and tolerable in heavily pre‐treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use.
影响因子：
12.8
作者：
Watanabe, T.;Mitsuhashi, M.;Sagawa, M.;Ri, M.;Suzuki, K.;Abe, M.;Ohmachi, K.;Nakagawa, Y.;Nakamura, S.;Chosa, M.;Iida, S.;Kizaki, M.
通讯作者：
Kizaki, M.