Efficacy of probiotics and trimebutine maleate for abemaciclib-induced diarrhea: A randomized, open-label phase II trial (MERMAID, WJOG11318B).

Humans Female Trimebutine / adverse effects Quality of Life Loperamide / adverse effects Breast Neoplasms / drug therapy Diarrhea / chemically induced Probiotics / therapeutic use Constipation / chemically induced
CDK4/6 inhibitor Constipation Diarrhea Probiotics Quality of life

Journal

Breast (Edinburgh, Scotland)
ISSN: 1532-3080
Titre abrégé: Breast
Pays: Netherlands
ID NLM: 9213011

Informations de publication

Date de publication:
Oct 2023
Historique:
received: 20 05 2023
revised: 06 07 2023
accepted: 07 07 2023
medline: 15 9 2023
pubmed: 17 7 2023
entrez: 17 7 2023
Statut: ppublish

Résumé

Abemaciclib-induced diarrhea (AID) impairs quality of life (QOL) and treatment adherence in patients with breast cancer. Supportive treatment with loperamide is associated with constipation. We hypothesized that probiotics and trimebutine maleate (TM) would decrease the frequency of AID without causing constipation. Hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer patients were randomized into the probiotic Bifidobacterium (A) or probiotic Bifidobacterium and TM (B) groups. Endocrine therapy, Abemaciclib and probiotic Bifidobacterium three times a day for 28 days, was administered to both arms. Arm B was treated with TM upon the onset of diarrhea. The primary endpoint was the percentage of patients who experienced grade ≥2 diarrhea. The secondary endpoints were safety, frequency, and duration of all-grade diarrhea; frequency of emesis and constipation; usage of loperamide; and health-related QOL/patient-reported outcome during the study. We evaluated whether the primary endpoint of each arm exceeded the predetermined threshold. Fifty-one patients completed treatment. Grade 2 diarrhea occurred in 52% and 50% of patients in Arm A and Arm B, respectively. One patient experienced grade 3 diarrhea in each arm. The median duration of grade2 diarrhea was 2 and 2.5day, and only one patient required dose reduction. Grade ≥2 constipation was observed in 4% of Arm A and 3.6% of Arm B. Probiotic Bifidobacterium or the combination of probiotic Bifidobacterium with TM did not decrease the incidence of grade 2 or greater diarrhea compared with historical control, although the grade 3 or greater diarrhea was reduced. jRCT (Japan registry of clinical trials). jRCTs031190154.

Sections du résumé

BACKGROUND BACKGROUND
Abemaciclib-induced diarrhea (AID) impairs quality of life (QOL) and treatment adherence in patients with breast cancer. Supportive treatment with loperamide is associated with constipation. We hypothesized that probiotics and trimebutine maleate (TM) would decrease the frequency of AID without causing constipation.
METHODS METHODS
Hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer patients were randomized into the probiotic Bifidobacterium (A) or probiotic Bifidobacterium and TM (B) groups. Endocrine therapy, Abemaciclib and probiotic Bifidobacterium three times a day for 28 days, was administered to both arms. Arm B was treated with TM upon the onset of diarrhea. The primary endpoint was the percentage of patients who experienced grade ≥2 diarrhea. The secondary endpoints were safety, frequency, and duration of all-grade diarrhea; frequency of emesis and constipation; usage of loperamide; and health-related QOL/patient-reported outcome during the study. We evaluated whether the primary endpoint of each arm exceeded the predetermined threshold.
RESULTS RESULTS
Fifty-one patients completed treatment. Grade 2 diarrhea occurred in 52% and 50% of patients in Arm A and Arm B, respectively. One patient experienced grade 3 diarrhea in each arm. The median duration of grade2 diarrhea was 2 and 2.5day, and only one patient required dose reduction. Grade ≥2 constipation was observed in 4% of Arm A and 3.6% of Arm B.
CONCLUSIONS CONCLUSIONS
Probiotic Bifidobacterium or the combination of probiotic Bifidobacterium with TM did not decrease the incidence of grade 2 or greater diarrhea compared with historical control, although the grade 3 or greater diarrhea was reduced.
CLINICAL TRIAL REGISTRATION BACKGROUND
jRCT (Japan registry of clinical trials). jRCTs031190154.

Identifiants

DOI: 10.1016/j.breast.2023.07.003 PMID: 37459790 PMC: PMC10512094
pubmed: 37459790
pii: S0960-9776(23)00518-0
doi: 10.1016/j.breast.2023.07.003
pmc: PMC10512094
pii:
doi:

Substances chimiques

abemaciclib 60UAB198HK
Trimebutine QZ1OJ92E5R
Loperamide 6X9OC3H4II

Types de publication

Randomized Controlled Trial Clinical Trial, Phase II Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

22-28

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Auteurs

Hiroko Masuda (H)

Department of Breast Surgical Oncology, Showa University, 1-5-8 Hatanodai Shinagawa-ku Tokyo 142-8555, Japan.

Yuko Tanabe (Y)

Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.

Hitomi Sakai (H)

Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo,142-8555, Japan.

Koji Matsumoto (K)

Medical Oncology Division, Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi-city Hyogo, 673-8558, Japan.

Akihiko Shimomura (A)

Department of Breast and Medical Oncology, National Center for Global Health and Medicine, 1-21-1 Toyama Shinjuku-ku, Tokyo, 162-8655, Japan.

Mihoko Doi (M)

Department of Clinical Oncology, Hiroshima Prefectural Hospital, 1-5-54 Ujinakanda Minami-ku Hiroshima-city Hiroshima, 734-8530, Japan.

Yasuo Miyoshi (Y)

Department of Surgery, Division of Breast and Endocrine Surgery, School of Medicine, Hyogo Medical University, 1-1 Mukogawa-cho Nishinomiya-city Hyogo, 663-8501, Japan.

Masato Takahashi (M)

Department of Breast Surgery, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-8648 Japan.

Yasuaki Sagara (Y)

Department of Breast Surgery, Sagara Hospital, Kagoshima, 3-31 Matsubara-cho Kagoshima City, Kagoshima 892-0833, Japan.

Shinya Tokunaga (S)

Department of Medical Oncology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori Miyakojima-ku Osaka 534-0021, Japan.

Tsutomu Iwasa (T)

Department of Medical Oncology, Kindai University, 3-4-1 Kowakae, Higashiosaka City Osaka 577-8502, Japan.

Naoki Niikura (N)

Department of Breast and Endocrine Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi Kanagawa 259-1193, Japan.

Kenichi Yoshimura (K)

Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Kasumi 1-2-3 Minami-ku, Hiroshima 734-8551, Japan.

Toshimi Takano (T)

Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.

Junji Tsurutani (J)

Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo,142-8555, Japan. Electronic address: tsurutaj@med.showa-u.ac.jp.

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