Phase I trial of continuous infusion interleukin-2 and doxorubicin in patients with refractory malignancies.

R M Bukowski, J S Sergi, G T Budd, S Murthy, R Tubbs, V Gibson, L Bauer, J Stanley, S Gautam, J Finke
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引用次数: 7

Abstract

A phase I trial was performed to assess the immunomodulatory activities, maximum tolerated doses, and the toxicity of recombinant interleukin-2 (rIL-2) administered in combination with doxorubicin to patients with refractory malignancies. Therapy was administered to successive cohorts of four to six patients who were treated at three different dose levels (1A, 1B, 2A). Levels 1-2 refer to doxorubicin (40 or 60 mg/m2) given as an intravenous (i.v.) bolus on day 1, and levels A-B refer to rIL-2 (1.0 or 3.0 x 10(6) U/m2) given as a continuous i.v. infusion on days 2-5, 9-12, and 16-19. Cycles were repeated every 28 days. Seventeen patients were entered in the trial. Dose limiting toxicity consisted of neutropenia, and the maximum tolerated dose (MTD) of the combination was doxorubicin 40 mg/m2 and rIL-2 3.0 x 10(6) U/m2. No objective responses were observed. Lymphocytosis related to rIL-2 occurred and flow cytometry demonstrated significant increases in the following subsets: CD3+CD25+HLADr+ and CD11b-CD16c+CD8-. Natural killer cell activity and lymphokine-activated killer (LAK) cell precursors were increased in patients treated at dose levels 1A and 1B (40 mg/m2 doxorubicin), but no consistent changes in LAK activity were noted. No clinical responses were seen and the overall toxicity of this combination was moderate to severe. Administration of doxorubicin prior to rIL-2 does not enhance the immunologic effects of rIL-2.

持续输注白介素-2和阿霉素治疗难治性恶性肿瘤的I期试验。
一项I期试验评估了重组白细胞介素-2 (il -2)与阿霉素联合应用于难治性恶性肿瘤患者的免疫调节活性、最大耐受剂量和毒性。4 - 6名患者连续接受3种不同剂量水平(1A、1B、2A)的治疗。水平1-2指的是第1天静脉注射的阿霉素(40或60mg /m2),水平a - b指的是il -2(1.0或3.0 × 10(6) U/m2),在第2-5天、第9-12天和第16-19天连续静脉输注。每28天重复一个周期。17名患者参加了试验。剂量限制性毒性为中性粒细胞减少,联合用药的最大耐受剂量(MTD)为阿霉素40 mg/m2和rIL-2 3.0 × 10(6) U/m2。未观察到客观反应。发生与rIL-2相关的淋巴细胞增多,流式细胞术显示以下亚群显著增加:CD3+CD25+HLADr+和CD11b-CD16c+CD8-。在剂量水平1A和1B (40mg /m2阿霉素)治疗的患者中,自然杀伤细胞活性和淋巴因子活化杀伤(LAK)细胞前体增加,但LAK活性没有一致的变化。未见临床反应,该组合的总体毒性为中度至重度。在使用il -2之前使用阿霉素不会增强il -2的免疫作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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