Defining the clinical benefits of adding a neurokinin-1 receptor antagonist to control chemotherapy-induced nausea and vomiting in moderately emetogenic chemotherapy: a systematic review and meta-analysis of the clinical practice guidelines for antiemesis 2023 from the Japan society of clinical oncology

Toshinobu Hayashi; Shun Yamamoto; Yoshiharu Miyata; Masayuki Takeda; Masakazu Abe; Makoto Wada; Keiko Iino; Tatsuo Akechi; Chiyo K Imamura; Ayako Okuyama; Keiko Ozawa; Yong-Il Kim; Hidenori Sasaki; Eriko Satomi; Ryuhei Tanaka; Takako Eguchi Nakajima; Naoki Nakamura; Junichi Nishimura; Mayumi Noda; Kazumi Hayashi; Takahiro Higashi; Narikazu Boku; Koji Matsumoto; Yoko Matsumoto; Kenji Okita; Nobuyuki Yamamoto; Kenjiro Aogi; Hirotoshi Iihara

doi:10.1007/s10147-024-02623-y

Defining the clinical benefits of adding a neurokinin-1 receptor antagonist to control chemotherapy-induced nausea and vomiting in moderately emetogenic chemotherapy: a systematic review and meta-analysis of the clinical practice guidelines for antiemesis 2023 from the Japan society of clinical oncology

Int J Clin Oncol. 2024 Nov;29(11):1616-1631. doi: 10.1007/s10147-024-02623-y. Epub 2024 Sep 11.

Authors

Toshinobu Hayashi¹, Shun Yamamoto², Yoshiharu Miyata³, Masayuki Takeda⁴, Masakazu Abe⁵, Makoto Wada⁶, Keiko Iino⁷, Tatsuo Akechi⁸, Chiyo K Imamura⁹, Ayako Okuyama¹⁰, Keiko Ozawa¹¹, Yong-Il Kim¹², Hidenori Sasaki¹³, Eriko Satomi¹⁴, Ryuhei Tanaka¹⁵, Takako Eguchi Nakajima¹⁶, Naoki Nakamura¹⁷, Junichi Nishimura¹⁸, Mayumi Noda¹⁹, Kazumi Hayashi²⁰, Takahiro Higashi²¹, Narikazu Boku²², Koji Matsumoto²³, Yoko Matsumoto²⁴, Kenji Okita²⁵, Nobuyuki Yamamoto²⁶, Kenjiro Aogi²⁷, Hirotoshi Iihara²⁸

Affiliations

¹ Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. [email protected].
² Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
³ Department of Artificial Intelligence and Digital Health Science, Kobe University Graduate School of Medicine, 7-1-48 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan.
⁴ Department of Cancer Genomics and Medical Oncology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan.
⁵ Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, Shizuoka, 431-3192, Japan.
⁶ Department of Psycho-Oncology, Osaka International Cancer Institute, 3-1-69 Chuo-Ku, Osaka, 541-8567, Japan.
⁷ School of Nursing, National College of Nursing, Japan, 1-2-1, Umezono, Kiyose, Tokyo, 204-8575, Japan.
⁸ Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
⁹ Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan.
¹⁰ Graduate School of Nursing Science, St. Luke's International University, 10-1 Akashi-Cho, Chuo-Ku, Tokyo, 104-0044, Japan.
¹¹ Division of Survivorship Institute for Cancer Control, National Cancer Center, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
¹² Division of Medical Oncology, Yodogawa Christian Hospital, 1-7-50 Kunijima, Higasiyodogawa-Ku, Osaka, Osaka, 533-0024, Japan.
¹³ Division of Medical Oncology, Hematology and Infectious Disease, Fukuoka University Hospital, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan.
¹⁴ Department of Palliative Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
¹⁵ Department of Pediatric Hematology/Oncology, International Medical Center, Saitama Medical University, 1398-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
¹⁶ Department of Early Clinical Development, Kyoto University Graduate School of Medicine, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
¹⁷ Department of Radiation Oncology, St. Marianna University, 2-16-1, Sugao, Miyamae, Kawasaki, 216-8511, Japan.
¹⁸ Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69, Osaka, 541-8567, Japan.
¹⁹ Non-Profit Organizaition Sasaeau-KaiAlpha, 518-7 Kawado-Cho, Chuo-Ku, Chiba, Chiba, 260-0802, Japan.
²⁰ Department of Clinical Oncology and Hematology, Jikei University School of Medicine, 3-25-8 Nishi-Shinnbashi Minatoku, Tokyo, 105-8461, Japan.
²¹ Department of Public Health and Health Policy, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
²² Department of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, 4-6-1 Shiroganedai, Minato-Ku, Tokyo, 108- 8639, Japan.
²³ Division of Medical Oncology, Hyogo Cancer Center, 13-70 Kitaoji-Cho, Akashi, Hyogo, 673-0021, Japan.
²⁴ Non-Profit Organization Ehime Cancer Support Orange-No-Kai, 3-8-24 Furukawaminami, Matsuyama, Ehime, 790-0943, Japan.
²⁵ Department of Surgery, Otaru Ekisaikai Hospital, 1-4-1 Inaho, Otaru, Hokkaido, 047-0032, Japan.
²⁶ Internal Medicine III, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama, 641-8509, Japan.
²⁷ Department of Breast Surgery, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-Machi, Matsuyama, Ehime, 791-0280, Japan.
²⁸ Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan.

PMID: 39259324
DOI: 10.1007/s10147-024-02623-y

Abstract

Background: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT₃RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC).

Methods: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT₃RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model.

Results: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events.

Conclusions: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy.

Keywords: Antiemetics; Carboplatin; Chemotherapy-induced nausea and vomiting; Moderately emetogenic chemotherapy; Neurokinin-1 receptor antagonist; Systematic review and meta-analysis.

Publication types

Systematic Review
Meta-Analysis

MeSH terms

Antiemetics* / therapeutic use
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Dexamethasone / therapeutic use
Humans
Japan
Medical Oncology / standards
Nausea* / chemically induced
Nausea* / drug therapy
Nausea* / prevention & control
Neoplasms / drug therapy
Neurokinin-1 Receptor Antagonists* / therapeutic use
Practice Guidelines as Topic
Quality of Life
Randomized Controlled Trials as Topic
Serotonin 5-HT3 Receptor Antagonists / therapeutic use
Vomiting* / chemically induced
Vomiting* / drug therapy
Vomiting* / prevention & control

Substances

Antiemetics
Antineoplastic Agents
Dexamethasone
Neurokinin-1 Receptor Antagonists
Serotonin 5-HT3 Receptor Antagonists