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Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients

Cancer Chemotherapy and Pharmacology volume 91, pages 481–490 (2023)Cite this article

Abstract

Purpose

Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients.

Methods

Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 h after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS).

Results

Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant.

Conclusion

Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.

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Availability of data and materials

The data that support the findings of the present study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

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Acknowledgements

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant No. JP20H01018 and JP21H04186. This manuscript has been released as a pre-print at Research Square (https://doi.org/10.21203/rs.3.rs-1414973/v1).

Funding

Yusuke Suzuki received financial support from the Japan Society for the Promotion of Science (JSPS) (KAKENHI, Grant No. JP20H01018 and JP21H04186).

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Authors and Affiliations

  1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Yusuke Suzuki, Takafumi Naito, Kaito Shibata & Junichi Kawakami

  2. Department of Pharmacy, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Takafumi Naito

  3. Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Seiji Hosokawa

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  1. Yusuke Suzuki
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  2. Takafumi Naito
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  4. Seiji Hosokawa
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Contributions

YS and TN conceptualized the study with input from JK. YS funded the study. YS and KS recruited patients and performed blood sampling with assistance from SH. SH evaluated clinical symptoms. YS and KS curated drug and serum marker results and analyzed and interpreted data with assistance of TN. YS and TN wrote the manuscript and all coauthors reviewed and contributed to the manuscript.

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Correspondence to Takafumi Naito.

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The authors declare there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical approval

The present study protocol was approved by the Ethics Committee of Hamamatsu University School of Medicine (17–102) and was conducted in accordance with the Declaration of Helsinki. Written consent obtained from each patient after explaining the purpose of the study and other information.

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

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Suzuki, Y., Naito, T., Shibata, K. et al. Associations of plasma aprepitant and its N-dealkylated metabolite with cachexia status and clinical responses in head and neck cancer patients. Cancer Chemother Pharmacol 91, 481–490 (2023). https://doi.org/10.1007/s00280-023-04537-4

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