Quan Walter D Y, Quan Francine M
Department of Medical Oncology, Division of Hematology/Oncology, Loma Linda University School of Medicine, 11234 Anderson Street, Loma Linda, CA 92354, USA.
Cancer Biother Radiopharm. 2009 Feb;24(1):1-6. doi: 10.1089/cbr.2008.0540.
High-dose interleukin-2 (IL-2), given via continuous intravenous (i.v.) infusion, induces lymphokine-activated killer (LAK) cell cytotoxicity against tumor cells. These LAKs exhibit enhanced cytotoxicity against tumor cells in vitro when they are subsequently pulsed with additional IL-2. Famotidine may increase LAK cytotoxicity against neoplastic cells by allowing for greater IL-2 uptake at the IL-2 receptor on lymphocytes. Twenty-three (23) patients received famotidine 20 mg i.v. twice per day and continuous-infusion IL-2 (18 MIU/m(2)/24 hours) for 72 hours, followed by a 24-hour rest, then 1-3 daily-pulse IL-2 doses of 18 MIU/m(2) over 15-30 minutes preceded by famotidine 20 mg i.v. Cycles were repeated every 3 weeks. The most common metastatic sites were lung, lymph node, and subcutaneous/soft tissue. The most common toxicities were fever, rigor, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and pulmonary edema. There were no treatment-related deaths. One (1) complete (4%) and 9 partial responses (39%) were seen (43% total response rate; 95% confidence interval: 22%-65%). Median survival for all patients is 13 months. The combination of famotidine and high-dose continuous infusion + pulse IL-2 is active in metastatic melanoma.
通过持续静脉输注给予高剂量白细胞介素-2（IL-2）可诱导淋巴因子激活的杀伤（LAK）细胞对肿瘤细胞的细胞毒性。这些LAK细胞在随后用额外的IL-2脉冲处理后，在体外对肿瘤细胞表现出增强的细胞毒性。法莫替丁可能通过使淋巴细胞上的IL-2受体摄取更多的IL-2来增加LAK对肿瘤细胞的细胞毒性。23例患者接受法莫替丁20mg静脉注射，每日两次，持续输注IL-2（18MIU/m²/24小时）72小时，随后休息24小时，然后在15 - 30分钟内静脉注射20mg法莫替丁后，每日1 - 3次脉冲给予18MIU/m²的IL-2。每3周重复一个周期。最常见的转移部位是肺、淋巴结和皮下/软组织。最常见的毒性反应是发热、寒战、恶心/呕吐、低磷血症、低血压、肌酐升高和肺水肿。没有与治疗相关的死亡。观察到1例完全缓解（4%）和9例部分缓解（39%）（总缓解率43%；95%置信区间：22% - 65%）。所有患者的中位生存期为13个月。法莫替丁与高剂量持续输注+脉冲IL-2联合应用对转移性黑色素瘤有效。
