Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
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发表时间：
2000-03
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通讯作者：
M. Varterasian;R. Mohammad;Muhammad Shurafa;Kim Hulburd;Pamela A. Pemberton;Dorothy H. Rodriguez;Virginia Spadoni;David Eilender;A. Murgo;Nathan R. Wall;M. Dan;A. Al-Katib
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作者：
M. Varterasian;R. Mohammad;Muhammad Shurafa;Kim Hulburd;Pamela A. Pemberton;Dorothy H. Rodriguez;Virginia Spadoni;David Eilender;A. Murgo;Nathan R. Wall;M. Dan;A. Al-Katib
苔藓抑素1是1982年从海洋苔藓虫Bugula neritina中分离得到的天然产物，目前正在对许多恶性肿瘤进行评估。25例复发、低度非霍奇金淋巴瘤或慢性淋巴细胞白血病（CLL）患者接受苔藓抑素1，每2周持续输注72小时，剂量为120 μ g/m2/疗程。在单独接受苔藓抑素1治疗期间发生疾病进展的患者可以参加可行性研究，在完成苔藓抑素1输注后立即接受长春新碱静脉推注给药。在3例患者的组中，长春新碱剂量递增如下：水平1，0.5 mg/m2;水平2，1.0 mg/m2;和水平3，1.4 mg/m2，所有患者的长春新碱剂量上限为2.0 mg。苔藓抑素1单独导致一个完全缓解和两个部分缓解。9例患者接受苔藓抑素1和长春新碱序贯治疗。以2 mg剂量添加长春新碱是可行的，并引起预期的剂量相关感觉神经病变。通过流式细胞术分析前和后苔藓抑素1处理的外周血淋巴细胞的表型分析显示上调的CD 11 c/CD 22的共表达的CD 20 + B细胞在两个4 CLL患者的研究，这是一致的CLL细胞分化为毛细胞表型的体外研究结果。
Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.