Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: Cancer and leukemia Group B protocol 50206
Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: Cancer and leukemia Group B protocol 50206
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DOI：
10.1080/10428190701411458
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Bartlett, Nancy L.
中科院分区：
文献类型：
--
作者：
Blum, Kristie A.;Johnson, Jeffrey L.;Bartlett, Nancy L.
已在患者源性Reed -斯滕贝格细胞和霍奇金淋巴瘤（HL）细胞系中描述了核因子-κ B（NF-κ B）的组成性激活，并有助于HL的增殖和存活。用硼替佐米治疗性抑制蛋白酶体可通过阻止I κ B降解来抑制核NF-κ B的过度表达，I κ B降解将NF-κ B隔离在细胞质中。为了评价这一假设，癌症和白血病组B（CALGB）在复发性或难治性经典HL患者中开展了一项多机构II期硼替佐米单药治疗试验。30例患者在第1、4、8、11天和每21天接受硼替佐米1.3 mg/m2，中位数为2个周期（范围，1 - 8）。患者接受了大量的预治疗，中位数为4种既往治疗，83%的患者既往接受过移植。未观察到缓解，9例患者病情稳定，21例患者病情进展。中位无进展生存期和总生存期分别为1.4个月[95% CI，（1.28，1.91）]和14.8个月[95% CI（11.2，22.3）]。15例患者发生3 - 4级不良事件，主要是血小板减少症。因此，尽管耐受性良好，但1.3 mg/m2硼替佐米每两周给药一次对复发性/难治性经典HL无单药活性。
Constitutive activation of nuclear factor-kappa B (NF-kappa B) has been described in patient-derived Reed - Sternberg cells and Hodgkin lymphoma ( HL) cell lines and contributes to the proliferation and survival of HL. Therapeutic inhibition of the proteasome with bortezomib may inhibit over-expression of nuclear NF-kappa B by preventing degradation of I kappa B, which sequesters NF-kappa B in the cytoplasm. To evaluate this hypothesis, the Cancer and Leukemia Group B (CALGB) conducted a multi-institutional phase II trial of single agent bortezomib in patients with relapsed or refractory classical HL. Thirty patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11 and every 21 days for a median of 2 cycles ( range, 1 - 8). Patients were heavily pre-treated with a median of four prior therapies, and 83% were previously transplanted. No responses were observed, 9 patients had stable disease, and 21 progressed. The median progression-free and overall survivals were 1.4 months [95% CI, ( 1.28, 1.91)] and 14.8 months [95% CI ( 11.2, 22.3)], respectively. Grade 3 - 4 adverse events, primarily thrombocytopenia, occurred in 15 patients. Therefore, although well tolerated, 1.3 mg/m(2) bortezomib administered biweekly has no single agent activity in relapsed/ refractory classical HL.