Mackean M J, Kerr D, Lesko M, Svedberg A, Hansson F, Jodrell D, Cassidy J
CRC Medical Oncology Department, Beatson Oncology Centre, Glasgow, UK.
Br J Cancer. 1998 Dec;78(12):1620-3. doi: 10.1038/bjc.1998.732.
Thirty-one patients with advanced renal carcinoma or malignant melanoma were treated in the first feasibility study of alpha-interferon (Roferon) and the new oral immunomodulating agent, Linomide. Linomide 5 mg or 10 mg p.o. daily was given for 2 weeks; alpha-interferon was then added at 3 MU s.c. three times weekly, escalating in each patient by 3 MU per week, if tolerable, up to 12 MJ. The combination was poorly tolerated with nausea, vomiting, somnolence and myalgia commonly reported. Adverse events accounted for treatment withdrawal in ten patients and contributed to withdrawal in four other patients. Treatment with Linomide alone in the first 2 weeks led to a significant increase in white blood cells, neutrophils and platelets. When alpha-interferon was added, the platelet count decreased significantly over the following 6 weeks. Nineteen patients had white cell phenotype and function measured. After 2 weeks of 5 mg Linomide, a transient but significant decrease in the absolute number of activated T-helper cells (CD4+DR+) was observed. No changes in natural killer (NK) cell number or activity were observed. Twenty-two patients were evaluable for response. One with metastatic renal cell carcinoma had a complete response and six had stable disease. This study does not support the use of the combination because significant toxicity was seen without the anticipated immunological benefits.
在第一项关于α-干扰素（罗扰素）和新型口服免疫调节剂利诺米德的可行性研究中，对31例晚期肾癌或恶性黑色素瘤患者进行了治疗。每天口服利诺米德5毫克或10毫克，持续2周；然后添加α-干扰素，皮下注射300万单位，每周3次，若患者耐受，每周增加300万单位，直至1200万单位。该联合治疗耐受性差，常见恶心、呕吐、嗜睡和肌痛的报告。不良事件导致10例患者停止治疗，另有4例患者因不良事件而停药。前2周单独使用利诺米德治疗导致白细胞、中性粒细胞和血小板显著增加。添加α-干扰素后，血小板计数在接下来的6周内显著下降。对19例患者进行了白细胞表型和功能检测。服用5毫克利诺米德2周后，观察到活化辅助性T细胞（CD4+DR+）的绝对数量出现短暂但显著的下降。未观察到自然杀伤（NK）细胞数量或活性的变化。22例患者可评估疗效。1例转移性肾细胞癌患者出现完全缓解，6例患者病情稳定。本研究不支持使用该联合治疗方案，因为观察到显著的毒性反应，却未获得预期的免疫学益处。
