PHASE-I TRIAL OF A GENETICALLY-ENGINEERED INTERLEUKIN-2 FUSION TOXIN (DAB(486)IL-2) AS A 6-HOUR INTRAVENOUS-INFUSION IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

被引：20

作者：

PLATANIAS, LC

RATAIN, MJ

OBRIEN, S

LARSON, RA

VARDIMAN, JW

SHAW, JP

WILLIAMS, SF

BARON, JM

PARKER, K

WOODWORTH, TG

机构：

[1] Section of Hematology-Oncology, Departments of Medicine and Pathology, Committee on Clinical Pharmacology and Cancer Research Center, University of Chicago, Pritzker School of Medicine, Chicago, IL

[2] Seragen Incorporation, Hopkinton, MA

来源：

LEUKEMIA & LYMPHOMA | 1994年 / 14卷 / 3-4期

关键词：

PHASE I TRIAL; IL-2 FUSION TOXIN; DAB(486)IL-2; HEMATOLOGIC NEOPLASMS;

D O I：

10.3109/10428199409049676

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

DAB(486)IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB(486)IL-2, administered as a 6 hour continuous intravenous infusion on days 1, 2, 8, 9, 15, and 16 of each 28 day cycle. Cohorts of 3 to 6 patients were treated with escalating doses. The starting dose was 0. 1 mg/kg/day with increments of O.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, anemia, thrombocytopenia, fever, and creatinine elevation. A partial response of approximately nine months duration was observed in a patient with small cell lymphocytic non-Hodgkin's lymphoma, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB(486)IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.

引用

页码：257 / 262

页数：6

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