Conventional Therapy Combined With Quxie Capsule Modulating Gut Microbiome in Metastatic Colorectal Cancer Patients With the Third or Above Line Setting: Result From an Investigator-Initiated, Open-Label, Single-Arm, Phase II Study.

IF 2.9 3区医学 Q2 INTEGRATIVE & COMPLEMENTARY MEDICINE

Integrative Cancer Therapies Pub Date : 2024-01-01 DOI:10.1177/15347354241280390

Zhien Gu, Lei Wang, Jiawei Zhai Ma, Tong Zhang, Yufei Yang

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引用次数: 0

Abstract

Background: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)-a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)-has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting.

Methods: A Simon's Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform.

Results: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae, Eubacterium and Lachnospiraceae_UCG-001.

Conclusions: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2100053874).

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三线或三线以上转移性结直肠癌患者的常规治疗联合曲昔胶囊调节肠道微生物组：一项由研究者发起、开放标签、单臂、II 期研究的结果。

背景：在转移性结直肠癌（mCRC）患者中，Quxie Cap-sule（QX）--一种常规疗法（包括化疗、靶向治疗或支持治疗）的组合--与安慰剂相比，显示出显著的总体生存获益，并且可能具有抗肿瘤和增强免疫力的双重效果，这两种效果均由微生物组介导。在临床前模型中，QX 也显示出对结直肠癌的活性。本研究旨在描述 QX 对三线或三线以上患者的上述效果：本研究采用了西蒙最小二阶段 II 期设计，招募了二线治疗后病情进展的 mCRC 患者。患者接受常规治疗加 QX，直至疾病进展或出现不可接受的毒性反应。在为期 1 个月的干预前后，我们采集了患者的粪便样本，通过 16s rRNA 测序方法进行微生物组分析。并通过生物信息分析平台对干预1个月前后的微生物组进行分析：结果：15 名患者入组，10 名患者中有 7 名的肠道微生物组分析结果显示，PFS 超过 3.7 个月。微生物群落的属种分析表明，常规治疗加 QX 后，Lachnospiraceae_UCG-001（0.04% vs 1.06%，P = .02249）的比例显著增加，而 Alistipes（2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) 的比例在干预后明显下降。LEFSe分析表明，干预后，样本与未分类的拉赫ospiraceae、Eubacterium和Lachnospiraceae_UCG-001高度相关：结论：具有潜在致癌作用的肠道细菌减少，而Lachnospiraceae等肠道抗癌细菌的丰度增加，这可能部分解释了常规治疗结合QX如何影响结肠癌的癌变和肿瘤进展：试验注册：中国临床试验注册中心（ChiCTR2100053874）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Integrative Cancer Therapies 医学-全科医学与补充医学

CiteScore

4.80

自引率

3.40%

发文量

审稿时长

>12 weeks

期刊介绍： ICT is the first journal to spearhead and focus on a new and growing movement in cancer treatment. The journal emphasizes scientific understanding of alternative medicine and traditional medicine therapies, and their responsible integration with conventional health care. Integrative care includes therapeutic interventions in diet, lifestyle, exercise, stress care, and nutritional supplements, as well as experimental vaccines, chrono-chemotherapy, and other advanced treatments. Contributors are leading oncologists, researchers, nurses, and health-care professionals.