A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas.

The Korean Journal of Hematology Pub Date : 2012-03-01 Epub Date: 2012-03-28 DOI:10.5045/kjh.2012.47.1.53
Jeong Eun Kim, Dok Hyun Yoon, Geundoo Jang, Dae Ho Lee, Shin Kim, Chan-Sik Park, Jooryung Huh, Won Seog Kim, Jinny Park, Jae Hoon Lee, Soon Il Lee, Cheolwon Suh
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引用次数: 12

Abstract

Background: Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).

Methods: Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m(2) bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.

Results: Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m(2). In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.

Conclusion: Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.

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晚期弥漫性大b细胞淋巴瘤患者每2周使用硼替佐米加CHOP (CHOP-14)的I/II期研究。
背景:硼替佐米靶向核因子-κB活化和细胞周期控制的分子失调,这是弥漫性大b细胞淋巴瘤(DLBCL)的特征。我们每2周(CHOP-14)评估硼替佐米与剂量密集环磷酰胺、阿霉素、长春新碱和强的松(CHOP)联合治疗的安全性和有效性。方法:纳入未经治疗的DLBCL患者。在CHOP-14方案的基础上,在第1天和第4天分别给药1.0、1.3和1.6 mg/m(2)硼替佐米进行I期剂量递增研究,以确定最大耐受剂量(MTD)和剂量限制性毒性(DLT)。第4-13天给予Lenograstim 5µg/kg/d。来自I期研究的硼替佐米剂量用于II期研究。结果:分别有9名和37名患者入组I期和II期研究。II期结果分析(40例患者)包括I期试验最后一次MTD剂量队列中的3例患者的数据。在I期试验中,任何剂量的硼替佐米均未观察到DLT;因此,推荐剂量为1.6 mg/m(2)。在II期,总缓解率为95%(完全缓解:80%;部分缓解:15%)。40例患者中有9例出现3级感觉神经病变,22例需要至少减少一次剂量。3例患者因严重的神经病变未能完成预期的6个疗程的治疗。结论:硼替佐米联合CHOP-14治疗未经治疗的DLBCL患者非常有效,但在许多情况下,需要改变剂量或方案以减少神经毒性。
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