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

这项方案的目的是检查免疫效果 左旋咪唑使用现代检测技术以确定是否 交替剂量和时间表的左旋咪唑给药将产生 最大限度的免疫调节。左旋咪唑也被联合使用。 对于干扰素-伽马，一种细胞因子，其免疫调节特性 在生物研究所进行的前两次试验中得到了很好的定义 响应修改器计划。 左旋咪唑每隔一天口服一次，每次四次 不同的剂量水平。两组患者有资格进入 这场审判。一组患有晚期转移性疾病，另一组患有晚期转移性疾病 辅助组(辅助组)在手术治疗后给予相应的治疗。 患者无疾病。左旋咪唑单独每隔一天给药一次 总共有六剂。休息10天后，相同剂量的左旋咪唑 与干扰素-γ联合使用，剂量为0.1 mg/m sq 与左旋咪唑同一天每隔一天皮下注射一次。 左旋咪唑10 mg/kg剂量对小鼠的剂量限制性毒性 两组患者均接受治疗。最大耐受量被定义为5毫克/公斤 每隔一天。在这个剂量水平下，治疗耐受性良好 左旋咪唑单独和左旋咪唑加干扰素伽马治疗。 单用左旋咪唑可剂量依赖性地增加血清新喋呤和 可溶性白介素2受体水平。单核细胞的激活 高亲和力Fc受体CD64的表达增加， 通过增加HLAABC和HLADR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 interferon-gamma, a cytokine whose immunomodulatory properties have been well defined in two previous trials conducted at the Biological Response Modifiers Program. Levamisole was administered orally every other day at one of four different dose levels. Two groups of patients 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 patient disease free. Levamisole alone was administered every other day for a total of six doses. After ten-day rest, the same dose of levamisole was given in combination with interferon-gamma 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 patients. The maximum-tolerated dose was defined as 5 mg/kg every other day. At this dose level, treatment was well tolerated with levamisole alone and with levamisole plus interferon gamma. Levamisole alone produced dose-dependent increases in serum neopterin and soluble interleukin-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.