Wang Hsiu-Tzu, Yu Yung-Luen, Lo Wen-Jyi, Lin Mei-Chen, Chu Chien-Lun, Chen Chia-Yu, Wang Sing-Ting, Chiu Chang-Fang, Bai En-Jia, Bai Li-Yuan
Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, 2, Yude road, North district, Taichung, 404327, Taiwan.
Institute of Translational Medicine and New Drug Development, China Medical University, Taichung, 406040, Taiwan.
Int J Clin Oncol. 2025 Dec 10. doi: 10.1007/s10147-025-02930-y.
Malignant ascites occur in 10-15% of patients with gastrointestinal tract cancers. The abundance of immune cells in the peritoneum and ascitic fluid, along with the immunosuppressive environment created by cancer cells, suggests the potential utility of intraperitoneal (IP) immune checkpoint inhibitors for controlling malignant ascites.
Patients with gastrointestinal or pancreaticobiliary tract cancer and cytologically confirmed malignant ascites received IP nivolumab. Twenty mg of nivolumab diluted in 100 mL of saline was infused into the peritoneal cavity over 10 min following paracentesis. IP treatment was repeated after each subsequent paracentesis until deemed ineffective by the treating physician, upon the occurrence of unacceptable toxicity, or discontinued at the patient's request. This study was registered at ClinicalTrials.gov (NCT05745233).
The median age of the nine enrolled patients was 55 years. Underlying malignancies included pancreatic (n = 4), biliary tract (n = 3), and gastric cancers (n = 2). After a median of 3 (range: 2-5) treatment cycles, seven patients (77.8%) showed a clinical response, as evidenced by reduced ascitic fluid and prolonged intervals between paracenteses. The only adverse effect observed was grade 1 tenderness at the puncture sites. Reduction in tumor cell count in ascites, rather than changes in the total lymphocyte count or lymphocyte subpopulations, correlated with clinical response. Responders consistently exhibited increased vascular endothelial growth factor A and decreased interleukin-1α levels following nivolumab administration.
Intraperitoneal administration of nivolumab effectively controlled malignant ascites with minimal adverse effects. However, further validation in a larger cohort is required.
恶性腹水发生于10% - 15%的胃肠道癌症患者中。腹膜和腹水中免疫细胞丰富，加上癌细胞营造的免疫抑制环境，提示腹腔内（IP）免疫检查点抑制剂在控制恶性腹水中具有潜在效用。
患有胃肠道或胰胆管癌且经细胞学确诊为恶性腹水的患者接受IP纳武利尤单抗治疗。在穿刺放腹水后10分钟内，将20毫克纳武利尤单抗稀释于100毫升生理盐水中注入腹腔。每次后续穿刺放腹水后重复IP治疗，直至治疗医生认为无效、出现不可接受的毒性反应或患者要求停药。本研究已在ClinicalTrials.gov注册（NCT05745233）。
9名入组患者的中位年龄为55岁。潜在恶性肿瘤包括胰腺癌（n = 4）、胆管癌（n = 3）和胃癌（n = 2）。中位3个（范围：2 - 5个）治疗周期后，7名患者（77.8%）显示出临床反应，表现为腹水减少和穿刺放腹水间隔时间延长。观察到的唯一不良反应是穿刺部位1级压痛。腹水中肿瘤细胞计数的减少与临床反应相关，而非总淋巴细胞计数或淋巴细胞亚群的变化。纳武利尤单抗给药后，有反应者始终表现出血管内皮生长因子A增加和白细胞介素 - 1α水平降低。
腹腔内给予纳武利尤单抗可有效控制恶性腹水，且不良反应最小。然而，需要在更大队列中进行进一步验证。
