持续输注重组白细胞介素-2与间歇注射重组干扰素-α 2a的I期试验：临床效果

Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon-alpha 2a: clinical effects.

作者信息

Bukowski R M, Murthy S, Sergi J, Budd G T, McKeever S, Medendorp S V, Tubbs R, Gibson V, Finke J

机构信息

Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Ohio 44195-5236.

出版信息

J Biol Response Mod. 1990 Dec;9(6):538-45.

PMID:2074440

Abstract

A phase I trial of high-dose continuous infusion rIL-2 over 5 days and i.m. recombinant human interferon-alpha (rHuIFN-alpha 2a) three times weekly in 23 patients with advanced malignancy has been completed. Cohorts of patients were treated at three different dose levels: rIL-2 3.0 x 10(6) u/m2 plus rHuIFN-alpha 2a either 5.0 or 10.0 x 10(6) u/m2, and rIL-2 4.5 x 10(6) u/m2 plus rHuIFN-alpha 2a 5.0 x 10(6) u/m2 over 4 weeks. Dose-limiting toxicity consisted of pulmonary and neurologic side effects, and the maximal tolerated dose was 3.0 x 10(6) u/m2 on days 1-5 or rIL-2, and 10.0 x 10(6) u/m2 three times weekly of rHuIFN-alpha 2a. Four partial responses (renal carcinoma, three; endometrial carcinoma, one) were seen. In conclusion, toxicity of this schedule of rIL-2 and rHuIFN-alpha 2a was significant, but manageable. Further investigation is needed to define the antitumor activity of this combination.

摘要

一项针对23例晚期恶性肿瘤患者的I期试验已完成，该试验为期5天高剂量持续输注重组白细胞介素-2（rIL-2）并每周三次肌肉注射重组人干扰素-α（rHuIFN-α 2a）。患者被分为三组，接受三种不同剂量水平的治疗：rIL-2 3.0×10⁶ U/m²加rHuIFN-α 2a 5.0或10.0×10⁶ U/m²，以及4周内rIL-2 4.5×10⁶ U/m²加rHuIFN-α 2a 5.0×10⁶ U/m²。剂量限制性毒性包括肺部和神经方面的副作用，最大耐受剂量为第1 - 5天的rIL-2 3.0×10⁶ U/m²，以及每周三次的rHuIFN-α 2a 10.0×10⁶ U/m²。观察到4例部分缓解（肾癌3例；子宫内膜癌1例）。总之，rIL-2和rHuIFN-α 2a这种给药方案的毒性显著，但可控制。需要进一步研究来确定该联合用药的抗肿瘤活性。