Mego Michal, Danis Radoslav, Chovanec Jozef, Jurisova Silvia, Bystricky Branislav, Porsok Stefan, Konkolovsky Peter, Vaclav Vladimir, Wagnerova Maria, Streško Marian, Brezinova Bibiana, Rečková Mária, Sutekova Dagmar, Pazderova Natalia, Novisedlakova Mária, Zomborska Eva, Ciernikova Sona, Svetlovska Daniela, Drgona Lubos
Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.
Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Front Oncol. 2023 Aug 4;13:1168654. doi: 10.3389/fonc.2023.1168654. eCollection 2023.
The incidence of irinotecan-induced diarrhea varies between 60-90%, by which the incidence of severe diarrhea is 20-40%. The objective of this phase III trial was to determine the effectiveness of the probiotic mixture containing , BB-12 and , LGG in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer patients due to a reduction in the activity of intestinal beta-D-glucuronidase.
From March 2016 to May 2022, a total of 242 patients with colorectal cancer starting a new line of irinotecan-based therapy were registered to the study in 11 cancer centers in Slovakia. Patients were randomized in a ratio 1:1 to probiotic formula vs. placebo that was administered for 6 weeks. Each capsule of Probio-Tec BG-Vcap-6.5 contained 2.7x10 colony-forming units (CFU) of 2 lyophilized probiotic strains , BB-12 (50%) and GG, LGG (50%).
Administration of probiotics compared to placebo was not associated with a significant reduction of grade 3/4 diarrhea (placebo arm 11.8% vs. probiotic arm 7.9%, p=0.38). Neither the overall incidence of diarrhea (46.2% vs. 41.2%, p=0.51) nor the incidence of enterocolitis (3.4% vs. 0.9%, p=0.37) was different in the placebo vs. probiotic arm. Subgroup analysis revealed that patients with colostomy had higher incidence of any diarrhea and grade 3/4 diarrhea in the placebo arm compared to the probiotic arm (48.5% vs. 22.2%, p=0.06 and 15.2% vs. 0%, p=0.06, respectively). Moreover, patients on probiotic arm had significantly better diarrhea-free survival (HR = 0.41, 95%CI 0.18 - 0.95, p=0.05) and needed less loperamide (p=0.01) compared to patients on placebo arm. We did not observe any infection caused by probiotic strains used in this study.
This study failed to achieve its primary endpoint, and results suggest a lack of benefit of administered probiotic formula for the prevention of irinotecan-induced diarrhea. However, subgroup analysis suggests a possible benefit in patients with colostomy.
伊立替康所致腹泻的发生率在60% - 90%之间，其中严重腹泻的发生率为20% - 40%。这项III期试验的目的是确定含有BB - 12和LGG的益生菌混合物在预防转移性结直肠癌患者伊立替康所致腹泻方面的有效性，其作用机制是降低肠道β - D - 葡萄糖醛酸酶的活性。
2016年3月至2022年5月，斯洛伐克11个癌症中心共纳入242例开始新的基于伊立替康治疗方案的结直肠癌患者进行本研究。患者按1:1随机分为益生菌配方组和安慰剂组，给药6周。每粒Probio - Tec BG - Vcap - 6.5胶囊含有2种冻干益生菌菌株（BB - 12占50%，LGG占50%）的2.7×10菌落形成单位（CFU）。
与安慰剂相比，给予益生菌并未显著降低3/4级腹泻的发生率（安慰剂组为11.8%，益生菌组为7.9%，p = 0.38）。安慰剂组与益生菌组在腹泻的总发生率（46.2%对41.2%，p = 0.51）和小肠结肠炎的发生率（3.4%对0.9%，p = 0.37）方面均无差异。亚组分析显示，与益生菌组相比，造口术患者在安慰剂组中任何腹泻和3/4级腹泻的发生率更高（分别为48.5%对22.2%，p = 0.06；15.2%对0%，p = 0.06）。此外，与安慰剂组患者相比，益生菌组患者的无腹泻生存期显著更长（风险比=0.41，95%置信区间0.18 - 0.95，p = 0.05），且需要的洛哌丁胺更少（p = 0.01）。我们未观察到本研究中使用的益生菌菌株引起的任何感染。
本研究未达到其主要终点，结果表明给予益生菌配方对预防伊立替康所致腹泻无益处。然而，亚组分析提示对造口术患者可能有益。
