Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial.
Effect of Exercise or Metformin on Biomarkers of Inflammation in Breast and Colorectal Cancer: A Randomized Trial.
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DOI：
10.1158/1940-6207.capr-20-0188
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Meyerhardt JA
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文献类型：
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作者：
Brown JC;Zhang S;Ligibel JA;Irwin ML;Jones LW;Campbell N;Pollak MN;Sorrentino A;Cartmel B;Harrigan M;Tolaney SM;Winer EP;Ng K;Abrams TA;Sanft T;Douglas PS;Hu FB;Fuchs CS;Meyerhardt JA
观察性研究报告，体力活动和二甲双胍与癌症患者临床结局改善相关。炎症是一种假设介导这些关联的生物学机制。在这项II期、多中心、2×2析因试验中，139名完成标准治疗的乳腺癌和结直肠癌患者被随机分配至4个治疗组之一，持续12周：单独运动、单独二甲双胍、运动和二甲双胍或对照。炎症结局包括高敏C反应蛋白（hs-CRP）、可溶性肿瘤坏死因子α受体2（sTNF-αR2）和白细胞介素6（IL-6）。主要建模策略评价了使用广义线性混合模型定量的试验药物被估量。与对照组相比，单独运动降低了hs-CRP：−30.2%（95% CI：−50.3，−1.0）和IL-6：−30.9%（95% CI：−47.3，−9.5）;但没有改变sTNF-αR2：1.0%（95% CI：−10.4，13.9）。与对照组相比，二甲双胍单药治疗未改变hs-CRP：−13.9%（95% CI：−40.0，23.4）、sTNF-αR2：−10.4%（95% CI：−21.3，2.0）或IL-6：−22.9%（95% CI：−42.3，2.0）。与对照组相比，运动和二甲双胍降低sTNF-αR2：−13.1%（95% CI：−22.9，−1.0）和IL-6：−38.7%（95% CI：−52.3，−18.9）;但未改变hs-CRP：−20.5%（95% CI：−44.0，12.7）。运动与二甲双胍联合治疗对hs-CRP、sTNF-αR2或IL-6无协同作用。在基线体力活动低且无2型糖尿病的乳腺癌和结直肠癌幸存者中，运动和二甲双胍减少了与癌症复发和死亡率相关的炎症指标。
Observational studies report that physical activity and metformin are associated with improved clinical outcome in patients with cancer. Inflammation is one biological mechanism hypothesized to mediate these associations. In this phase II, multi-center, 2×2 factorial trial, 139 patients with breast and colorectal cancer who completed standard therapy were randomized to one of four treatment groups for 12 weeks: exercise alone, metformin alone, exercise and metformin, or control. Inflammation outcomes included high sensitivity C-reactive protein (hs-CRP), soluble tumor necrosis factor alpha receptor two (sTNF-αR2), and interleukin 6 (IL-6). The primary modeling strategy evaluated the trial product estimand that was quantified using a generalized linear mixed model. Compared with control, exercise alone reduced hs-CRP: −30.2% (95% CI: −50.3, −1.0) and IL-6: −30.9% (95% CI: −47.3, −9.5); but did not change sTNF-αR2: 1.0% (95% CI: −10.4, 13.9). Compared with control, metformin alone did not change hs-CRP: −13.9% (95% CI: −40.0, 23.4), sTNF-αR2: −10.4% (95% CI: −21.3, 2.0), or IL-6: −22.9% (95% CI: −42.3, 2.0). Compared with control, exercise and metformin reduced sTNF-αR2: −13.1% (95% CI: −22.9, −1.0) and IL-6: −38.7% (95% CI: −52.3, −18.9); but did not change hs-CRP: −20.5% (95% CI: −44.0, 12.7). The combination of exercise and metformin was not synergistic for hs-CRP, sTNF-αR2, or IL-6. In survivors of breast and colorectal cancer with low baseline physical activity and without type 2 diabetes, exercise and metformin reduced measures of inflammation that are associated with cancer recurrence and mortality.