Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial

Abstract Background Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We...

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Main Authors: Chao Deng, Qing Liu, Meng Yang, Hui-juan Cui, Yang Ge, Qin Li, Shi-jie Zhu, Guo-wang Yang, Zhi-guo Zhang, Yu Gao, Yan-ni Lou, Li-qun Jia
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Language:English
Published: BMC 2024-11-01
Series:Chinese Medicine
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Online Access:https://doi.org/10.1186/s13020-024-01025-6
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author Chao Deng
Qing Liu
Meng Yang
Hui-juan Cui
Yang Ge
Qin Li
Shi-jie Zhu
Guo-wang Yang
Zhi-guo Zhang
Yu Gao
Yan-ni Lou
Li-qun Jia
author_facet Chao Deng
Qing Liu
Meng Yang
Hui-juan Cui
Yang Ge
Qin Li
Shi-jie Zhu
Guo-wang Yang
Zhi-guo Zhang
Yu Gao
Yan-ni Lou
Li-qun Jia
author_sort Chao Deng
collection DOAJ
description Abstract Background Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1). Methods In this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA. Results 101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1–3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue. Conclusions SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal “Trials” in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).
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spelling doaj-art-0d99041e16174103aac2d1340798dd8f2025-08-20T02:13:40ZengBMCChinese Medicine1749-85462024-11-0119111210.1186/s13020-024-01025-6Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trialChao Deng0Qing Liu1Meng Yang2Hui-juan Cui3Yang Ge4Qin Li5Shi-jie Zhu6Guo-wang Yang7Zhi-guo Zhang8Yu Gao9Yan-ni Lou10Li-qun Jia11Department of Medical Oncology, Integrated Traditional Chinese and Western Medicine, China-Japan Friendship HospitalDepartment of Medical Oncology, Integrated Traditional Chinese and Western Medicine, China-Japan Friendship HospitalDepartment of Respiratory and Critical Care Medicine, China-Japan Friendship HospitalDepartment of Medical Oncology, Integrated Traditional Chinese and Western Medicine, China-Japan Friendship HospitalDepartment of Medical Oncology, Beijing Chao-Yang Hospital, Capital Medical UniversityDepartment of Medical Oncology, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Medical Oncology, Wangjing Hospital of China Academy of Traditional Chinese MedicineDepartment of Medical Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityDepartment of Medical Oncology, Beijing Daxing District People’s HospitalDepartment of Traditional Chinese Medicine, Peking University Third HospitalDepartment of Medical Oncology, Integrated Traditional Chinese and Western Medicine, China-Japan Friendship HospitalDepartment of Medical Oncology, Integrated Traditional Chinese and Western Medicine, China-Japan Friendship HospitalAbstract Background Irinotecan is a standard chemotherapeutic agent in small cell lung cancer (SCLC), however, as a common adverse reaction, diarrhea limits the use of irinotecan. Shengjiang Xiexin decoction (SXD) has been used in various gastrointestinal diseases in China two thousand years ago. We designed this clinical trial to supply more evidences on the use of SXD as prophylaxis for irinotecan-induced diarrhea, especially for high-risk population predicted by gene testing of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1). Methods In this clinical trial, 120 patients with SCLC were recruited from six hospitals in China. They received two cycles of chemotherapy, meanwhile they were randomized to receive SXD or placebo for 14 days of oral administration in each cycle of chemotherapy. The primary outcome is the incidence of diarrhea. And secondary outcomes include the the degree of diarrhea and neutropenia, the number of chemotherapy cycles with diarrhea, first occurrence time and duration of diarrhea. To evaluate the effect of SXD on the intestine, a rat model with delayed-onset diarrhea induced by irinotecan was established, and the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, anti-inflammatory factors including IL-10, TGF- β in jejunal tissue was detected by ELISA. Results 101 patients (53 in SXD group, 48 in placebo group) completed the trial. The incidence of diarrhea in SXD group and placebo group were 26.42% (14/53) and 52.08% (25/48), respectively (P < 0.05), and the degree of diarrhea also had significant differences (P < 0.05). In UGT1A1 high-risk population, the incidence of diarrhea in two groups were 9.09% and 66.67% (P < 0.05), but there was no significant differences in UGT1A1 low-risk population. The incidence of neutropenia with degree 1–3 between two groups was 20.75% vs 20.83%, 13.21% vs 18.57%, 9.43% vs 20.83% (P < 0.05). No severe adverse events were reported in any group. And animal studies had shown SXD reduced content of IL-1β, IL-6, TNF-α, increased content of IL-10, TGF-β in jejunum tissue. Conclusions SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal “Trials” in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).https://doi.org/10.1186/s13020-024-01025-6Irinotecan-induced diarrheaRandomized controlled trialShengjiang Xiexin decoction
spellingShingle Chao Deng
Qing Liu
Meng Yang
Hui-juan Cui
Yang Ge
Qin Li
Shi-jie Zhu
Guo-wang Yang
Zhi-guo Zhang
Yu Gao
Yan-ni Lou
Li-qun Jia
Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
Chinese Medicine
Irinotecan-induced diarrhea
Randomized controlled trial
Shengjiang Xiexin decoction
title Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
title_full Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
title_fullStr Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
title_full_unstemmed Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
title_short Efficacy and safety of Shengjiang Xiexin decoction on irinotecan-induced diarrhea in small cell lung cancer patients: a multicenter, randomized, double-blind, placebo-controlled trial
title_sort efficacy and safety of shengjiang xiexin decoction on irinotecan induced diarrhea in small cell lung cancer patients a multicenter randomized double blind placebo controlled trial
topic Irinotecan-induced diarrhea
Randomized controlled trial
Shengjiang Xiexin decoction
url https://doi.org/10.1186/s13020-024-01025-6
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