Department of Medicine, The Cancer Institute of New Jersey, UMDNJ-RWJMS, New Brunswick NJ, USA.
J Transl Med. 2010 Feb 24;8:20. doi: 10.1186/1479-5876-8-20.
To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA)/interferon-alpha2b (IFN) with paclitaxel (TAX), or mitoxantrone, estramustine and vinorelbine (MEV) will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC).
70 patients were treated with either MEV (Arm A) in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B). Patients were assessed for response, toxicity, quality of life (QOL), and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC).
The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR) 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d.), and a significantly lower level of QOL than Arm A (p = 0.01). As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03).
Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy.
CDR0000067865.
为了验证以下假说，我们用 13-顺式维甲酸（CRA）/干扰素-α2b（IFN）联合紫杉醇（TAX），或米托蒽醌、雌莫司汀和长春瑞滨（MEV）对转移性去势抵抗性前列腺癌（CRPC）患者进行 Bcl-2 调节，检测其是否具有临床活性。
70 名患者接受 MEV（A 组）三周周期或 CRA/IFN/TAX 八周周期治疗（B 组）。评估患者的反应、毒性、生活质量（QOL）以及治疗对周围血单核细胞（PBMC）中 Bcl-2 水平的影响。
A 组和 B 组的 PSA 缓解率分别为 50%和 23%，可测量疾病缓解率（CR+PR）分别为 14%和 15%，中位总生存期分别为 19.4 个月和 13.9 个月。A 组和 B 组分别有 18 名和 2 名患者出现短暂的 4 级中性粒细胞减少症，7 名和 1 名患者出现 3 至 4 级血栓形成。B 组患者在第 9/10 周（0.71 标准差）报告 QOL 有明显下降，且 QOL 明显低于 A 组（p = 0.01）。正如假设的那样，只有 B 组患者的 CRA/IFN 治疗后 Bcl-2 水平下降（p = 0.03）。
MEV 治疗耐受性良好，对 CRPC 患者具有临床活性。鉴于 CRA/IFN/TAX 对 QOL 的不良影响，有必要研究其他针对 Bcl-2 家族蛋白的新型药物。在合作组中测量 Bcl-2 蛋白的可行性是产生假说的基础，并支持进一步研究作为 Bcl-2 靶向治疗的标志物。
CDR0000067865。
