Jourdan Eric, Leblond Veronique, Maisonneuve Hervé, Benhadji Karim A, Hossain Anwar M, Nguyen Tuan S, Wooldridge James E, Moreau Philippe
Centre Hospitalier Regional Universitaire de Nîmes , Nîmes , France.
Leuk Lymphoma. 2014 Sep;55(9):2013-7. doi: 10.3109/10428194.2013.861066. Epub 2014 May 2.
Enzastaurin is an oral serine/threonine kinase inhibitor of the protein kinase C (PKC) and phosphatidylinositol 3 (PI3) kinase/Akt pathways that induces apoptosis in multiple myeloma (MM) cell lines in a caspase-independent manner. A phase II study was conducted to assess response rate, time to progression (TTP), safety and biomarker association with clinical outcomes after monotherapy with the PKC inhibitor enzastaurin in previously treated patients with MM. Eligible patients (n = 14) were treated with enzastaurin 250 mg twice daily after receiving loading doses on day 1. One minimal response was observed. The median TTP was 5.11 months. There were two grade 3 adverse events, anemia and prolonged QTc interval, and no grade 4 adverse events. Single-agent enzastaurin was well tolerated but not effective in this heavily pretreated population with MM.
恩杂鲁胺是一种口服的丝氨酸/苏氨酸激酶抑制剂，可抑制蛋白激酶C（PKC）和磷脂酰肌醇3（PI3）激酶/Akt信号通路，以不依赖半胱天冬酶的方式诱导多发性骨髓瘤（MM）细胞系凋亡。开展了一项II期研究，以评估蛋白激酶C抑制剂恩杂鲁胺单药治疗既往接受过治疗的MM患者后的缓解率、疾病进展时间（TTP）、安全性以及生物标志物与临床结局的相关性。符合条件的患者（n = 14）在第1天接受负荷剂量后，每日两次服用250 mg恩杂鲁胺。观察到1例最小缓解。中位TTP为5.11个月。有2例3级不良事件，即贫血和QTc间期延长，无4级不良事件。单药恩杂鲁胺耐受性良好，但在这类接受过大量治疗的MM患者中无效。
