Distribution of therapeutic monoclonal antibodies into ascites in advanced gastric cancer patients with peritoneal metastasis: case reports and literature review
Distribution of therapeutic monoclonal antibodies into ascites in advanced gastric cancer patients with peritoneal metastasis: case reports and literature review
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治疗性单克隆抗体在晚期胃癌腹膜转移患者腹水中的分布：病例报告和文献复习
DOI：
10.1007/s00280-022-04479-3
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发表时间：
2022
影响因子：
3
通讯作者：
Homma Masato
中科院分区：
文献类型：
--
作者：
Kaneko Takuya;Doki Kosuke;Yamada Takeshi;Yamamoto Yoshiyuki;Moriwaki Toshikazu;Suzuki Yoshiharu;Homma Masato
治疗性单克隆抗体，包括ramucirumab和nivolumab，被用于治疗晚期胃癌（AGC）。恶性腹水常伴有腹膜转移。然而，治疗性单克隆抗体在腹水中的分布尚未得到充分的研究。方法测定3例伴有大量腹水的AGC患者血清和腹水中拉穆单抗或纳武单抗的浓度及总IgG。当日取血清和腹水标本，评价单克隆抗体浓度的腹水/血清比（A/S）。最后一次输注时间与治疗性单克隆抗体的A/S比之间的关系使用本研究和文献中的15个数据集进行检测。结果大量腹水中检测到ramucirumab和nivolumab （A/S比为0.24-0.35，nvolumab为0.17-0.55）。治疗性单克隆抗体的A/S比与末次输注时间呈正相关（r= 0.747）。采用穿刺去除腹水分别消除了注射ramucirumab和nivolumab的至少15.3%-30.3%和5.2-27.4%。内源性IgG和治疗性单克隆抗体分布在腹水中；IgG的A/S比值为0.22 ~ 0.45。结论治疗性单克隆抗体（包括ramucirumab和nivolumab）在AGC患者大量腹水中与内源性IgG共存。在这些患者中，腹水潴留及其清除可能导致拉穆单抗和纳武单抗的全身药物暴露减少。
BackgroundTherapeutic 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.MethodsWe 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.ResultsRamucirumab 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.ConclusionOur 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.