IMMUNOMODULATION OF INTERLEUKIN-2 BY CYCLOPHOSPHAMIDE - A PHASE-IB TRIAL

被引:13
作者
ABRAMS, JS
EISEMAN, JL
MELINK, TJ
SRIDHARA, R
HIPONIA, DJ
BELL, MM
BELANI, CP
ADLER, WH
AISNER, J
机构
[1] NIA,GERONTOL RES CTR,BALTIMORE,MD 21224
[2] UNIV MARYLAND,MED CTR,COLL PK,MD 20742
[3] UNIV MARYLAND,CTR CANC,DIV MED ONCOL,COLL PK,MD 20742
[4] UNIV MARYLAND,CTR CANC,DIV DEV THERAPEUT,COLL PK,MD 20742
来源
JOURNAL OF IMMUNOTHERAPY | 1993年 / 14卷 / 01期
关键词
CYCLOPHOSPHAMIDE; INTERLEUKIN-2; LAK CELLS; IMMUNOMODULATION; CANCER;
D O I
10.1097/00002371-199307000-00008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The objective of this phase IB trail was to determine if cyclophosphamide (CY) could enhance the immune effects of interleukin-2 (IL-2), and if it could, was there an optimal immunomodulatory dosage. IL-2 alone at 30 million IU/m2 thrice weekly for 6 weeks or in combination with varying dosages of CY (300, 600, and 1,200 mg/m2) administered 3 days before IL-2 and repeated 3 weeks later was given to consecutive cohorts of patients (at least five per group) with advanced malignancies of varying types. To gauge the immune effects of the treatment, the variation in the amount of lymphokine-activated killer (LAK) cells generated in the peripheral blood mononuclear cells of patients and in a control group of normal volunteers was measured weekly over 7 consecutive weeks. Other immune parameters [natural killer cells (NK), peripheral blood eosinophils and lymphocytes, cell surface markers, soluble IL-2 receptor, and IL-2 antibodies] were also closely followed to study if they correlated with the degree of LAK activity. The group of patients that received low-dosage CY (300 mg/m2) and IL-2 produced the highest and most sustained levels of LAK and NK activity (p < 0.05) when compared with the cohorts receiving IL-2 alone or to those receiving the higher dosages of CY. No other immune parameter showed a significant difference between the groups. Although low-dosage CY does increase the LAK activity seen with IL-2, only randomized clinical trials can determine if this enhancement will improve tumor responses.
引用
收藏
页码:56 / 64
页数:9
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