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Distribution of therapeutic monoclonal antibodies into ascites in advanced gastric cancer patients with peritoneal metastasis: case reports and literature review

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Abstract

Background

Therapeutic monoclonal antibodies, including ramucirumab and nivolumab, are used to treat advanced gastric cancer (AGC). Malignant ascites is often accompanied by peritoneal metastasis in AGC patients. However, the distribution of therapeutic monoclonal antibodies into ascites has yet to be adequately investigated.

Methods

We determined serum and ascites concentrations of ramucirumab or nivolumab and total IgG in three AGC patients with massive ascites. When serum and ascites samples were obtained on the same day, the ascites-to-serum ratio (A/S ratio) of the concentration of monoclonal antibodies was evaluated. The relationship between time after last infusion and the A/S ratio of therapeutic monoclonal antibodies was examined using 15 datasets from the present study and the literature.

Results

Ramucirumab and nivolumab were detected in massive ascites at considerable amounts (A/S ratios of 0.24–0.35 for ramucirumab and 0.17–0.55 for nivolumab). A positive correlation was detected between the A/S ratios of the therapeutic monoclonal antibodies and the time after last infusion (r = 0.747). Removal of ascites using paracentesis eliminated at least 15.3%–30.3% and 5.2–27.4% of the injected ramucirumab and nivolumab, respectively. Endogenous IgG, as well as therapeutic monoclonal antibodies, were distributed into ascites; the A/S ratios for IgG were 0.22–0.45.

Conclusion

Our results suggest that therapeutic monoclonal antibodies, including ramucirumab and nivolumab, are distributed into massive ascites in AGC patients concomitantly with endogenous IgG. In these patients, retention of ascites and its removal may result in decreased systemic drug exposure to ramucirumab and nivolumab.

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Fig. 1
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Data availability

The data of the current study are available from the corresponding author upon reasonable request.

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Funding

This research was supported in part by a Grant-in-Aid for Scientific research (C) (grant No. 22K06718) from the Japan Society for the Promotion of Science to K. Doki.

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Authors and Affiliations

  1. Department of Pharmacy, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan

    Takuya Kaneko, Kosuke Doki & Masato Homma

  2. Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan

    Takuya Kaneko, Kosuke Doki, Yoshiharu Suzuki & Masato Homma

  3. Division of Gastroenterology, University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan

    Takeshi Yamada, Yoshiyuki Yamamoto & Toshikazu Moriwaki

Authors
  1. Takuya Kaneko
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  2. Kosuke Doki
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  3. Takeshi Yamada
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  4. Yoshiyuki Yamamoto
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  5. Toshikazu Moriwaki
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  6. Yoshiharu Suzuki
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  7. Masato Homma
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Correspondence to Kosuke Doki.

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The authors declare no conflict of interest.

Ethical approval

This study was approved by the Ethical Committee of the University of Tsukuba Hospital (Tsukuba, Japan).

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Kaneko, T., Doki, K., Yamada, T. et al. Distribution of therapeutic monoclonal antibodies into ascites in advanced gastric cancer patients with peritoneal metastasis: case reports and literature review. Cancer Chemother Pharmacol 90, 421–426 (2022). https://doi.org/10.1007/s00280-022-04479-3

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  • DOI: https://doi.org/10.1007/s00280-022-04479-3

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