Department of Internal and Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Clin Cancer Res. 2021 Jul 1;27(13):3784-3792. doi: 10.1158/1078-0432.CCR-20-4918. Epub 2021 Apr 21.
Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer.
In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics).
Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group ( = 12) had a higher DCR at 12 weeks ( = 0.035) compared with the autologous group ( = 12), longer median OS of 365 versus 227 days [HR = 0.38; 95% confidence interval (CI), 0.14-1.05; = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT ( = 0.010) indicating proper engraftment of the donor microbiota.
FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.
恶病质是一种多因素综合征，与癌症患者的生存预后不良相关，且受肠道微生物群的影响。我们研究了粪便微生物群移植（FMT）对晚期胃食管腺癌患者恶病质和治疗反应的影响。
在阿姆斯特丹大学医学中心进行的一项双盲、随机、安慰剂对照试验中，我们将 24 例转移性 HER2 阴性胃食管腺癌恶病质患者分为异体 FMT（健康肥胖供体）或自体 FMT 组，在姑息性化疗（卡培他滨和奥沙利铂）之前进行。主要目的是评估异体 FMT 对饱腹感的影响。次要结果是恶病质的其他特征，以及疾病控制率（DCR）、总生存期（OS）、无进展生存期（PFS）和毒性。最后，还对 FMT 对肠道微生物群组成（宏基因组测序）和代谢物（非靶向代谢组学）的影响进行了探索性分析。
异体 FMT 并未改善任何恶病质结局。异体组（n = 12）患者的 12 周时 DCR 更高（P = 0.035），与自体组（n = 12）相比，中位 OS 更长（365 天比 227 天，HR = 0.38；95%CI，0.14-1.05；P = 0.057），PFS 更长（204 天比 93 天，HR = 0.50；95%CI，0.21-1.20；P = 0.092）。异体 FMT 后，异体组患者粪便微生物群组成发生显著变化（P = 0.010），表明供体微生物群的适当定植。
在一线化疗前给予健康肥胖供体的 FMT 并未影响恶病质，但可能改善转移性胃食管腺癌患者的反应和生存。这些结果为更大规模的 FMT 试验提供了依据。
