Abstract：
OBJECTIVE: Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy.
METHODS: This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.
RESULTS: Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).
CONCLUSIONS: Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.
METHODS: This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.
RESULTS: Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).
CONCLUSIONS: Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.
摘要：
目的：米诺环素在临床前模型中抑制化疗诱导的神经炎症，但它对癌症幸存者的影响尚不清楚。这项研究评估了米诺环素对情感行为的纵向影响，认知功能，以及接受化疗的乳腺癌（BC）女性的炎症。
方法：这是一个试点项目，双盲,口服米诺环素(100mgBID)与安慰剂治疗开始I-III期BC化疗的女性化疗引起的情感障碍的随机对照试验。参与者在化疗前一周接受米诺环素或安慰剂，继续通过周期4（C4）。流行病学研究抑郁量表（CES-D）和状态特质焦虑量表（STAI）在基线时进行评估，每个化疗周期（C1-C4），化疗后2-3周（化疗结束），化疗后6个月（6M）作为主要结果。还进行了基于症状严重程度的CES-D和STAI的亚组分析。还评估了自我报告的认知和血清炎症标志物的变化。
结果：57名妇女参加了这项研究，55名妇女完成了这项研究。除白细胞介素-8（p≤0.03）外，炎症标志物的变化，认知功能,CES-D,从基线到任何周期或化疗后时间点，STAI在组间均无显著差异（均p>0.05），调整基线分数。米诺环素改善了血清白细胞介素-8从基线到C4和6M的增加(p<0.05)。与安慰剂相比，使用米诺环素治疗的有抑郁症症状的亚组（基线CES-D>=16）的CES-D评分从基线降低至6M（p=0.01）。
结论：尽管IL-8减弱，米诺环素在接受化疗的BC幸存者队列中并未改变自我报告的情感症状或认知。米诺环素对化疗前有抑郁症症状的BC幸存者的影响值得进一步研究。
方法：这是一个试点项目，双盲,口服米诺环素(100mgBID)与安慰剂治疗开始I-III期BC化疗的女性化疗引起的情感障碍的随机对照试验。参与者在化疗前一周接受米诺环素或安慰剂，继续通过周期4（C4）。流行病学研究抑郁量表（CES-D）和状态特质焦虑量表（STAI）在基线时进行评估，每个化疗周期（C1-C4），化疗后2-3周（化疗结束），化疗后6个月（6M）作为主要结果。还进行了基于症状严重程度的CES-D和STAI的亚组分析。还评估了自我报告的认知和血清炎症标志物的变化。
结果：57名妇女参加了这项研究，55名妇女完成了这项研究。除白细胞介素-8（p≤0.03）外，炎症标志物的变化，认知功能,CES-D,从基线到任何周期或化疗后时间点，STAI在组间均无显著差异（均p>0.05），调整基线分数。米诺环素改善了血清白细胞介素-8从基线到C4和6M的增加(p<0.05)。与安慰剂相比，使用米诺环素治疗的有抑郁症症状的亚组（基线CES-D>=16）的CES-D评分从基线降低至6M（p=0.01）。
结论：尽管IL-8减弱，米诺环素在接受化疗的BC幸存者队列中并未改变自我报告的情感症状或认知。米诺环素对化疗前有抑郁症症状的BC幸存者的影响值得进一步研究。
