伏立诺他治疗复发性或难治性惰性非霍奇金淋巴瘤和套细胞淋巴瘤的II期研究

2024-05-15 15:48:31来源：医脉通阅读：115次

文献标题：Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

文献出处：JCO 2.14, 2011

期刊影响因子：17.793

PMID：21300924

为检测伏立诺他治疗复发性或难治性惰性淋巴瘤患者的有效性和患者的耐受性，我们对口服这一组蛋白和蛋白去乙酰酶抑制剂进行了II期研究。研究揭示口服伏立诺他是治疗FL和MZL的有力药物，安全性可接受。还有必要对其和其它激动剂联用进行进一步研究。

在这项开放标签的II期研究(NCT00253630)中，入组的有复发性和难治性滤泡淋巴瘤(FL)患者、边缘带淋巴瘤(MZL)患者、外套细胞淋巴瘤(MCL)患者，这些患者的前期治疗均≤ 4次。所有患者均口服伏立诺他，用法为200mg，第1-14天每日两次，21天为一个疗程，治疗直至疾病恶化或患者不能耐受药物毒性。主要终点是客观反应率 (ORR)，次要终点是无进展生存(PFS)，到进展时间，有效时期，安全性和耐受性。

35名入组患者的反应全部具有可评估性。伏立诺他疗程中位数为9。ORR为29%（5例完全反应[CR],5例部分反应[PR]）。17名FL患者中，ORR为47%（4例CR，4例PR）。9名MZL患者有两例有反应（1例CR，1例PR），尽管有1例患者病情稳定保持了26个月，9名MCL患者无1例发生有效反应。FL、MCL、MZL患者的中位PFS分别为15.6、5.9、18.8个月.此药长期治疗耐受性好，最常见的3级不良反应是血小板减少症、贫血、白细胞减少症和疲劳。

医脉通推荐英文摘要
JCO 2.7, 2011.doi: 10.1200/JCO.2010.32.1398

Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

Mark Kirschbaum, Paul Frankel, Leslie Popplewell

( The City of Hope, Duarte)

Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.

Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.

Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.

Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.