Margolin K, Aronson F R, Sznol M, Atkins M B, Gucalp R, Fisher R I, Sunderland M, Doroshow J H, Ernest M L, Mier J W
City of Hope National Medical Center, Department of Medical Oncology, Duarte, California 91010-0269.
J Immunother Emphasis Tumor Immunol. 1994 Feb;15(2):147-53. doi: 10.1097/00002371-199402000-00009.
Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.
白细胞介素（IL-4）是一种多能细胞因子，可刺激活化T细胞增殖，并在动物系统中对人类肾肿瘤具有抗肿瘤活性。在I期试验中，IL-4的剂量高达20微克/千克时仍可耐受，剂量限制性毒性包括发热、液体潴留、鼻塞和粘膜炎。我们报告了两项分别针对30例转移性恶性黑色素瘤患者和19例晚期肾癌患者的IL-4 II期试验结果。IL-4每8小时静脉注射一次，共14剂，分两个5天疗程，中间间隔9天。最初的27例患者接受800微克/平方米的剂量治疗，但其中3例患者出现心脏毒性后，剂量降至600微克/平方米。1例转移性黑色素瘤患者出现完全缓解（持续时间≥30个月）。肾癌患者中未见缓解。最常见的副作用是发热、恶心、不适、鼻塞和腹泻。可逆性肝肾功能障碍也很常见。低血压不常见，但因液体潴留导致的短暂体重增加很常见。主要的危及生命的毒性是心脏和胃肠道毒性。2例患者观察到疑似心脏缺血，1例患者出现心包炎，2例患者出现心律失常。3例患者出现严重上消化道出血，无局部肿瘤证据。我们得出结论，按此方案以最大耐受剂量单独给予IL-4时，对肾癌或黑色素瘤不具有显著活性。
