West Clinic, Memphis, TN, USA.
Br J Haematol. 2014 Jul;166(1):91-7. doi: 10.1111/bjh.12853. Epub 2014 Mar 27.
This open-label, phase II study investigated whether enzastaurin, a protein kinase C-beta (PKCβ) inhibitor, had activity in patients with grade 1 or 2 follicular lymphoma (FL). Adults with grade 1 or 2 FL who had no more than one prior treatment received oral enzastaurin continuously for up to 3 years. Of the 66 patients who received enzastaurin, 53 were evaluable for response. Overall response rate (ORR, primary efficacy endpoint) was 26.4% (3.8% complete response). Median (95% confidence interval) progression-free survival, time to response, and duration of response were 18.1 (11.5-28.3), 4.9 (2.8-8.1), and 22.3 (8.8-not applicable) months, respectively. In patients with tumour tissue available for biomarker analysis, ORRs in low versus high PKCβ2 expression groups were 41.7% and 8.3%, respectively (P = 0.041). The most common, mainly low-grade drug-related adverse events were fatigue (25.8%), diarrhoea (25.8%), nausea (18.2%), and chromaturia (18.2%). Four (6.1%) patients had Grade 3 toxicity and one (1.5%) patient had Grade 4 toxicity. Enzastaurin demonstrated limited clinical activity in grade 1 or 2 FL. Patients with low PKCβ2 expression in tumours had higher ORR than those with high PKCβ2 expression. Enzastaurin was well tolerated with mostly grade 1 or 2 toxicities. Further studies may be warranted in select patient populations.
这项开放标签、二期研究旨在探讨蛋白激酶 C-β（PKCβ）抑制剂恩杂鲁胺在 1 或 2 级滤泡淋巴瘤（FL）患者中的疗效。无更多既往治疗史的 1 或 2 级 FL 成人患者接受口服恩杂鲁胺连续治疗，最长达 3 年。在接受恩杂鲁胺治疗的 66 例患者中，53 例可评估缓解情况。总体缓解率（ORR，主要疗效终点）为 26.4%（3.8%完全缓解）。中位（95%置信区间）无进展生存期、缓解时间和缓解持续时间分别为 18.1（11.5-28.3）、4.9（2.8-8.1）和 22.3（8.8-无法评估）个月。在有肿瘤组织进行生物标志物分析的患者中，低表达与高表达 PKCβ2 患者的 ORR 分别为 41.7%和 8.3%（P = 0.041）。最常见的、主要为低级别药物相关不良事件是疲劳（25.8%）、腹泻（25.8%）、恶心（18.2%）和尿色异常（18.2%）。4 例（6.1%）患者发生 3 级毒性，1 例（1.5%）患者发生 4 级毒性。恩杂鲁胺在 1 或 2 级 FL 中疗效有限。肿瘤中 PKCβ2 表达低的患者缓解率高于 PKCβ2 表达高的患者。恩杂鲁胺耐受性良好，大多数为 1 或 2 级毒性。在某些患者群体中可能需要进一步研究。
