Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH) , Bethesda, MD, USA.
Department of Clinical Research, Clinical Trial Innovations , Mountain View, CA, USA.
Expert Opin Investig Drugs. 2021 Feb;30(2):177-183. doi: 10.1080/13543784.2021.1863947. Epub 2021 Jan 11.
: In a Phase II study RRx-001 was combined with Etoposide platinum (EP) in previously platinum treated SCLC. We correlated expression of the M2 marker, CD206, on HLA-DR monocytes, a phenotype that correlates with a poor prognosis, with response to RRx-001. : Patients received 4 mg RRx-001 once weekly until progression followed by the start of EP (etoposide 100 mg/m IV on days 1-3 of a 21-day cycle and either cisplatin 80 mg/m IV on day 1 or carboplatin AUC 5-6 IV on day 1). Treatment continued until progression or intolerable toxicity. Peripheral blood was collected in Cell Preparation Tubes with sodium citrate from 14 patients for exploratory studies during screening and after therapy on Days 1, 8, and 15. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by centrifugation and multiparameter flow cytometric analysis was performed. : CD206 expression on HLA-DR monocytes was associated with response to chemotherapy and overall survival. : During treatment with RRx-001, reduced expression of the protumorigenic M2 marker CD206 on peripheral monocytes positively correlated with increased response and survival.
在一项 II 期研究中，RRx-001 与依托泊苷铂（EP）联合用于先前铂类治疗的 SCLC。我们将 HLA-DR 单核细胞上 M2 标志物 CD206 的表达与对 RRx-001 的反应相关联，该表型与预后不良相关。患者接受每周一次的 4 mg RRx-001 治疗，直至疾病进展，然后开始 EP 治疗（依托泊苷 100 mg/m2 IV，第 1-3 天，21 天周期，顺铂 80 mg/m2 IV 第 1 天或卡铂 AUC 5-6 IV 第 1 天）。治疗继续进行，直至疾病进展或无法耐受毒性。从 14 名患者在筛选期间和治疗后的第 1、8 和 15 天采集含有柠檬酸钠的 Cell Preparation Tubes 中的外周血进行探索性研究。通过离心从血液中分离外周血单核细胞（PBMCs），并进行多参数流式细胞术分析。HLA-DR 单核细胞上 CD206 的表达与对化疗的反应和总生存相关。在接受 RRx-001 治疗期间，外周单核细胞上促肿瘤 M2 标志物 CD206 的表达减少与反应增加和生存改善呈正相关。
