Quan Walter D Y, Walker Paul R, Picton Maria, Quan Francine M, King Linda A, Tyre Charley, Liles Darla K
Division of Hematology/Oncology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Cancer Biother Radiopharm. 2008 Oct;23(5):641-6. doi: 10.1089/cbr.2008.0522.
Daily short intravenous (i.v.) infusions (pulses) of interleukin-2 (IL-2) have been developed to decrease toxicity while maintaining anticancer activity of this agent against melanoma. Such IL-2 schedules have previously been shown to promote lymphokine-activated killer (LAK) cell activity. Famotidine may increase LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. We treated 16 patients with metastatic melanoma using pulse IL-2 18 (15 patients) or 9 million IU/M2 (1 patient) i.v. over 15-30 minutes preceded by famotidine 20 mg i.v. daily for 5 days on an oncology inpatient unit. Cycles were repeated every 3 weeks until disease progression. Patient characteristics were as follows: 11 males, median age, 66, median ECOG performance status, 1; common metastatic sites: lymph nodes, lungs, subcutaneous, liver, and bone. Median number of cycles received was 3. Overall, 93% of planned doses were delivered. Most common toxicities were hypomagnesemia, fever, rigors, hypophosphatemia, and nausea/emesis. Three (3) patients had partial responses (19% response rate; 95% confidence interval: 6%-44%). A fourth patient, after resection of residual disease, remains a surgical complete responder at > 12 months. Responses occurred in lung, liver, lymph nodes, bone, and subcutaneous sites. Median response duration was 7 months. Pulse IL-2 with famotidine has activity in melanoma.
每日短程静脉注射白细胞介素-2（IL-2）（脉冲式给药）已被研发出来，以降低毒性，同时维持该药物对黑色素瘤的抗癌活性。此前已证明，这种IL-2给药方案可促进淋巴因子激活的杀伤细胞（LAK）活性。法莫替丁可能通过增加淋巴细胞上IL-2受体对IL-2的内化作用来提高LAK活性。我们在肿瘤住院部对16例转移性黑色素瘤患者进行了治疗，先静脉注射20mg法莫替丁，每日1次，共5天，随后在15 - 30分钟内静脉注射IL-2，剂量为18×10⁶IU/m²（15例患者）或900万IU/m²（1例患者）。每3周重复一个周期，直至疾病进展。患者特征如下：男性11例，中位年龄66岁，中位东部肿瘤协作组（ECOG）体能状态评分为1；常见转移部位：淋巴结、肺、皮下组织、肝脏和骨骼。接受的中位周期数为3个。总体而言，93%的计划剂量得以给药。最常见的毒性反应为低镁血症、发热、寒战、低磷血症以及恶心/呕吐。3例患者出现部分缓解（缓解率19%；95%置信区间：6% - 44%）。第四例患者在切除残留病灶后，超过12个月仍为手术完全缓解者。缓解发生在肺、肝、淋巴结、骨和皮下部位。中位缓解持续时间为7个月。脉冲式IL-2联合法莫替丁对黑色素瘤有活性。
