PHASE IB TRIAL OF LEVAMISOLE ALONE AND IN COMBINATION WITH R-INTERFERON GAMMA

该方案的目的是检查免疫学效果， 左旋咪唑使用现代分析技术，以确定是否 左旋咪唑给药的替代剂量和时间表将产生 最大的免疫调节 左旋咪唑也与 IFN-γ是一种细胞因子，其免疫调节特性已被 在BRMP进行的前两次试验中得到了很好的定义。 左旋咪唑是 以4种不同剂量水平中的1种每隔一天口服给药。 两 患者组。有资格参加这项试验 一号群 晚期转移性疾病，第二组（辅助组）为 手术治疗后进行治疗，以使患者。疾病免费 左旋咪唑 每隔一天单独给药一次，总共给药6次。 后 10-休息日，给予相同剂量的左旋咪唑， 干扰素- 在0.1 mg/m2 sq的剂量下，每隔一天皮下注射， 和左旋咪唑是同一天 剂量限制性毒性在 两组患者均接受10 mg/kg剂量的左旋咪唑。 MTD定义为 5 mg/kg，隔日一次。 在该剂量水平下，治疗耐受性良好 单独使用左旋咪唑和左旋咪唑+IFN-γ。 左旋咪唑单药 血清新蝶呤和可溶性IL-2呈剂量依赖性增加 受体水平 单核细胞的活化通过增加 高亲和力Fc受体CD 64的表达，并通过增加 HLA-ABC和HLA-DR抗原的表达。

The purpose of this protocol was to examine the immunologic effects of levamisole using modern assay techniques in order to determine if an alternate dose and schedule of levamisole administration would produce maximal immunomodulation. Levamisole was also administered in combination with IFN-gamma, a cytokine whose immunomodulatory properties have been well defined in two previous trials conducted at the BRMP. Levamisole was administered orally every other day at 1 of 4 different dose levels. Two groups of pts. were eligible for entry on this trial. One group had advanced metastatic disease and the second group (adjuvant group) was treated after surgical therapy to render the pt. disease free. Levamisole alone was administered every other day for a total of 6 doses. After a 10-day rest, the same dose of levamisole was given in combination with IFN- at a dose of 0.1 mg/m sq. subcutaneously every other day on the same days as the levamisole. Dose-limiting toxicity was observed at the 10 mg/kg dose of levamisole in both groups of pts. The MTD was defined as 5 mg/kg every other day. At this dose level, treatment was well tolerated with levamisole alone and with levamisole + IFN-gamma. Levamisole alone produced dose-dependent increases in serum neopterin and soluble IL-2 receptor levels. Activation of monocytes was evidenced by increased expression of CD64, the high affinity Fc receptor, and by an increase in the expression of HLA-ABC and HLA-DR antigens.