Arellano Martha L, Borthakur Gautam, Berger Mark, Luer Jill, Raza Azra
Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA.
Department of Leukemia, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
Clin Lymphoma Myeloma Leuk. 2014 Dec;14(6):534-9. doi: 10.1016/j.clml.2014.04.007. Epub 2014 Jun 12.
Obatoclax mesylate is a small-molecule Bcl-2 homology domain-3 mimetic that neutralizes antiapoptotic Bcl-2-related proteins. We evaluated obatoclax in untreated MDS patients with anemia/thrombocytopenia.
Twenty-four patients with a bone marrow blast count of ≤ 10% and anemia (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 × 10(9)/L) were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks.
Response rate was 8% (2 patients; hematologic improvement). Disease stabilization/response was maintained ≥ 12 weeks in 50% (12 patients). Because the response rate was below a predetermined threshold, the study was terminated. Adverse events (any grade) included euphoric mood (63%; 15 patients), nausea (38%; 9 patients), and diarrhea (25%; 6 patients); Grade 3/4 adverse events included anemia (21%; 5 patients), thrombocytopenia (13%; 3 patients), and pneumonia (13%; 3 patients).
Obatoclax 60 mg every 2 weeks was feasible, but had limited first-line activity in MDS.
甲磺酸 obatoclax 是一种小分子 Bcl-2 同源结构域 3 模拟物，可中和抗凋亡的 Bcl-2 相关蛋白。我们对未经治疗的贫血/血小板减少的骨髓增生异常综合征（MDS）患者使用 obatoclax 进行了评估。
24 例骨髓原始细胞计数≤10%且伴有贫血（血红蛋白水平<10 g/dL）或血小板减少（血小板计数<50×10⁹/L）的患者符合入组标准，每 2 周接受一次 24 小时静脉输注 60 mg 甲磺酸 obatoclax 的治疗。
缓解率为 8%（2 例患者；血液学改善）。50%（12 例患者）的疾病稳定/缓解状态维持≥12 周。由于缓解率低于预定阈值，该研究终止。不良事件（任何级别）包括情绪愉悦（63%；15 例患者）、恶心（38%；9 例患者）和腹泻（25%；6 例患者）；3/4 级不良事件包括贫血（21%；5 例患者）、血小板减少（13%；3 例患者）和肺炎（13%；3 例患者）。
每 2 周使用 60 mg 甲磺酸 obatoclax 是可行的，但在 MDS 的一线治疗中活性有限。
