PHASE-II STUDIES OF RECOMBINANT HUMAN INTERLEUKIN-4 IN ADVANCED RENAL-CANCER AND MALIGNANT-MELANOMA
PHASE-II STUDIES OF RECOMBINANT HUMAN INTERLEUKIN-4 IN ADVANCED RENAL-CANCER AND MALIGNANT-MELANOMA
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DOI：
10.1097/00002371-199402000-00009
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发表时间：
1994-02-01
影响因子：
3.9
通讯作者：
WEISS, GR
中科院分区：
文献类型：
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作者：
MARGOLIN, K;ARONSON, FR;WEISS, GR
白细胞介素（IL）-4是一种多能性细胞因子，其刺激活化的T细胞的增殖，并且在动物系统中具有抗人肾肿瘤的抗肿瘤活性。在I期试验中，IL-4在高达20 μ g/kg的剂量下可以耐受，剂量限制性毒性包括发热、液体潴留、鼻充血和粘膜炎。我们报告了在30名转移性恶性黑色素瘤患者和19名晚期肾癌患者中进行的两项单独的IL-4 II期试验的结果。IL-4每8小时静脉内给药一次，共14剂，分为两个5天的疗程，间隔9天。最初的27名患者以800 μ g/m2的剂量进行治疗，但其中3名患者出现心脏毒性后，剂量降至600 μ g/m2。1例转移性黑色素瘤患者发生1例完全缓解（持续时间≥ 30个月）。在肾癌患者中未观察到反应。最常见的副作用是发热、恶心、不适、鼻塞和腹泻。可逆性肝肾功能不全也很常见。低血压是罕见的，但由于液体潴留一过性体重增加是常见的。主要危及生命的毒性为心脏和胃肠道毒性。在2名患者中观察到疑似心脏缺血，1名患者出现心包炎，2名患者出现心律失常。3例患者出现上消化道大出血，但无局部肿瘤证据。我们的结论是，IL-4，当作为一个单一的代理商在这个时间表上的最大耐受剂量，不具有有意义的活动在肾癌或黑色素瘤。
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 mu g/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 mu g/m(2), but after three of these patients developed cardiac toxicities, the dose was decreased to 600 mu g/m(2). One complete response occurred in a patient with metastatic melanoma (duration greater than or equal to 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.