The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected].
The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected].
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DOI：
10.1038/bjc.1991.64
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发表时间：
1991-02
影响因子：
8.8
通讯作者：
Gordon-Smith, E C
中科院分区：
文献类型：
--
作者：
Stein, R C;Malkovska, V;Morgan, S;Galazka, A;Aniszewski, C;Roy, S E;Shearer, R J;Marsden, R A;Bevan, D;Gordon-Smith, E C
35名晚期恶性疾病患者作为门诊患者通过每日一次自我皮下（s.c.）注射，每周5天，持续8周，然后是4周的观察期。在3个较低剂量下，患者未发生全身副作用。3例患者因不耐受（发热、皮疹、嗜睡、恶心和呕吐）需要从每日100 mcg剂量降低，1例患者因呼吸困难停药。我们在100 mcg剂量下观察到免疫学效应（但在较低剂量下未观察到）。这些包括（a）适度持续的淋巴细胞增多，（B）6例（共9例）患者中的嗜酸性粒细胞增多和（c）6例（共9例）患者中IL 2刺激的外周血淋巴细胞活化杀伤（LAK）细胞活性显著升高，平均达到治疗前水平的2.0倍（P <0.01）。9名接受每日100微克治疗的肾细胞癌患者中，有2名患者的部分缓解分别持续了4个月和9个月，另外3名患者的疾病稳定了至少3个月。低剂量长期皮下注射IL 2具有临床和免疫活性，与其他IL 2方案相比，它具有较小的毒性并且易于施用。这些特性使得低剂量s.c. IL 2适合在辅助环境中进行研究。
Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.