A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients
A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients
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DOI：
10.1007/s10549-019-05381-y
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Clemons, Mark
中科院分区：
文献类型：
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作者：
Arnaout, Angel;Robertson, Susan J.;Clemons, Mark
目的氯喹通过抑制细胞自噬和破坏细胞周期而具有抗肿瘤活性。本研究旨在通过一项随机、II期、双盲、安慰剂对照、术前机会窗试验评估氯喹单药对乳腺肿瘤细胞增殖的影响。方法将新诊断的乳腺癌患者按2：1的比例随机分为两组，分别服用氯喹500 mg/d或安慰剂2 ~ 6周。主要结果是治疗前和治疗后原发性乳腺癌细胞增殖指标（Ki 67）的相对变化。还评价了不良事件和毒性特征。结果从2015年9月至2016年12月，70例患者被随机分配[46例（66%）氯喹和24例（34%）安慰剂]。10名随机接受氯喹治疗的患者因不良事件退出研究。药物摄入的平均持续时间为15天（范围14-29天）。氯喹组和安慰剂组在药物治疗前后Ki 67指数的百分比变化（-0.4 vs. - 1.2，p = 0.088）或绝对变化（-2.0% vs. -5.2%，p = 0.066）方面均无显著差异。虽然不良反应很小，并且都被归类为1级，但这些影响足以导致近15%的患者停止治疗。结论：术前每日500 mg氯喹单药治疗对乳腺癌细胞增殖无显著影响。然而，它与毒性有关，可能会影响其在肿瘤学中的广泛应用。
Purpose Chloroquine has demonstrated anti-tumor activities through autophagy inhibition and cell cycle disruption. This study aimed to assess the effect of single-agent chloroquine on breast tumor cellular proliferation in a randomized, phase II, double-blind, placebo-controlled, pre-surgical window of opportunity trial. Methods Patients with newly diagnosed breast cancer were randomized 2:1 to chloroquine 500 mg daily or placebo for 2- to 6-weeks prior to their breast surgery. The primary outcome was the relative change in measures of proliferation (Ki67) in primary breast cancer cells pre- and post-treatment. Adverse events and toxicity profiles were also evaluated. Results From September 2015 to December 2016, 70 patients were randomized [46 (66%) chloroquine and 24 (34%) placebo]. Ten patients who were randomized to chloroquine withdrew from study due to adverse events. Mean duration of drug intake was 15 days (range 14-29 days). There were no significant differences between the chloroquine or placebo arms with respect to either the percentage change (- 0.4 vs. - 1.2, p = 0.088) or absolute change (- 2.0% vs. - 5.2%, p = 0.066) in Ki67 index pre- and post-drug treatment. Although adverse effects were minimal and all classified as grade 1, the effects were significant enough to cause nearly 15% of patients to discontinue therapy. Conclusions Treatment with single-agent chloroquine 500 mg daily in the preoperative setting was not associated with any significant effects on breast cancer cellular proliferation. It was, however, associated with toxicity that may affect its broader use in oncology.