Department of Haematology Wyong Hospital, Kanwal, Australia.
Clin Lymphoma Myeloma Leuk. 2013 Aug;13(4):398-403. doi: 10.1016/j.clml.2013.03.005. Epub 2013 Jun 14.
To assess the antitumor activity of enzastaurin in patients with non-Hodgkin lymphomas: T-cell lymphoma (n = 23): cutaneous and peripheral T-cell lymphoma; indolent B-cell lymphomas (n = 19): small lymphocytic, follicular grade 1 or 2, marginal zone lymphomas; and aggressive B-cell lymphomas (n = 15): follicular lymphomas grade 3, aggressive lymphoma with a clinical history. The primary objective was to determine overall tumor response. Secondary objectives included duration of response and safety.
In this multicenter, open-label, noncomparative, screening study conducted between December 2007 and February 2009, patients (≥ 18 years) who relapsed after ≥ 1 prior systemic treatment or who were intolerant to standard systemic therapy received 250 mg oral enzastaurin (125 mg tablets twice a day; a 1125-mg loading dose on day 1), in 28-day cycles for up to 2 years unless unacceptable toxicity or progressive disease occurred.
Responses were seen in follicular lymphomas grade 3 (1/5, 20.0%), cutaneous T-cell lymphoma (2/11, 18.2%), small lymphocytic lymphomas (1/7, 14.3%), and aggressive lymphoma with a clinical history (1/10, 10.0%) in this heavily pretreated patient population (median prior therapies range from 4 to 10). Most drug-related toxicities were grade 1/2, the most common being diarrhea, peripheral edema, and pruritus.
Enzastaurin was well tolerated but demonstrated modest responses across subgroups in this heavily pretreated patient population.
评估恩杂鲁胺在非霍奇金淋巴瘤患者中的抗肿瘤活性：T 细胞淋巴瘤（n=23）：皮肤和外周 T 细胞淋巴瘤；惰性 B 细胞淋巴瘤（n=19）：小淋巴细胞性、滤泡性 1 级或 2 级、边缘区淋巴瘤；侵袭性 B 细胞淋巴瘤（n=15）：滤泡性淋巴瘤 3 级、有临床病史的侵袭性淋巴瘤。主要目的是确定总体肿瘤反应。次要目标包括反应持续时间和安全性。
在这项于 2007 年 12 月至 2009 年 2 月进行的多中心、开放性、非对照、筛选研究中，接受过≥1 次先前系统治疗后复发或不耐受标准系统治疗的患者（≥18 岁）接受了 250mg 口服恩杂鲁胺（125mg 片剂，每日 2 次；第 1 天给予 1125mg 负荷剂量），每 28 天为一个周期，最长可达 2 年，除非出现无法耐受的毒性或疾病进展。
在滤泡性淋巴瘤 3 级（5 例中 1 例，20.0%）、皮肤 T 细胞淋巴瘤（11 例中 2 例，18.2%）、小淋巴细胞淋巴瘤（7 例中 1 例，14.3%）和有临床病史的侵袭性淋巴瘤（10 例中 1 例，10.0%）中观察到反应，这些患者的人群先前治疗中位数范围为 4 至 10 次。大多数药物相关毒性为 1/2 级，最常见的是腹泻、外周水肿和瘙痒。
在这个先前治疗过的患者人群中，恩杂鲁胺耐受性良好，但在各亚组中显示出适度的反应。
