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A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I-

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Summary

Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We wish to thank all the patients and medical staff who participated in this study.

Funding

This work was supported in part by JSPS KAKENHI Grant Number 20K07179. The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan

    Daiki Tsuji, Itsuki Yonezawa & Kunihiko Itoh

  2. Department of Pharmacy, Shizuoka General Hospital, Shizuoka, Japan

    Shigeru Nakagaki & Misa Osawa

  3. Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Kenichi Suzuki

  4. Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Takashi Yokokawa & Masahiro Hatori

  5. Faculty of Nursing, Japanese Red Cross College of Nursing, Tokyo, Japan

    Yohei Kawasaki

  6. Institute for Assistance of Academic and Education, IAAE, Kanagawa, Japan

    Takumi Yamaguchi

  7. Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

    Takashi Kawaguchi

  8. Pharmaceutical Department, National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan

    Takuma Matsumoto

  9. Department of Pharmacy, Hakodate Municipal Hospital, Hokkaido, Japan

    Yukio Sakata

  10. Department of Pharmacy, Seirei Hamamatsu General Hospital, Shizuoka, Japan

    Keisuke Yamamoto

  11. Department of Pharmacy, Wakayama Medical University Hospital, Wakayama, Japan

    Tomoyasu Nishimura

  12. Department of Pharmacy, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan

    Yuki Kogure

  13. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan

    Toshinobu Hayashi

  14. Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan

    Masaya Watanabe

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  1. Daiki Tsuji
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Contributions

Conception and design were performed by DT, SN, KS, TYo, YKa, TK, and MH. Acquisition of data was carried out by TM, YS, KY, TN, YKo, TH, MO, and MW. Statistical analysis and interpretation of the data were carried out by DT, IY, TYa, and YKa. Drafting of the article was carried out by DT, SN, IY, KI, and MW. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Daiki Tsuji.

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Ethical approval

This study was conducted in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects published by Japan’s Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare, Japan, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the institutional review board at the University of Shizuoka and each participating site.

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Informed consent was obtained from all individual participants included in the study.

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Tsuji, D., Nakagaki, S., Yonezawa, I. et al. A multicenter phase II trial of the triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for a cisplatin-containing regimen. - PATROL-I-. Invest New Drugs 42, 44–52 (2024). https://doi.org/10.1007/s10637-023-01414-y

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