PHASE 1 EVALUATION OF INTRATUMORAL INTERLEUKIN-1 ALPHA

本方案旨在确定最大耐受剂量 (MTD)白细胞介素-1（IL-1）α。 我们计划检查 在病灶内注射前和注射后获得的肿瘤标本 IL-1免疫组化技术。 肿瘤反应在 将监测注射病灶和远处转移。 将使用半对数增量的剂量递增方案， 确定MTD。 使用的起始剂量为0.001微克/千克， 患者目前正在以0.1微克/千克的剂量水平接受治疗。 迄今为止，IL-1 α的MTD尚未确定。 接受病灶内IL-1 α治疗的患者 与静脉注射IL-1 α观察到的毒性相比。 活检 注射IL-1的病变标本显示血管炎的证据， 注射肿瘤外血管周围的淋巴聚集体 结节和偶尔的血管在肿瘤本身。 肿瘤活检 已经显示出肿瘤内淋巴聚集的证据， 在治疗前活检标本上发现。 既不是局部的也不是系统的 抗肿瘤反应发生在15名患者的初始组中。

The purpose of this protocol is to determine the maximum tolerated dose (MTD) of intralesional interleukin-1 (IL-1) alpha. We plan to examine tumor specimens obtained before and after intralesional injection of IL-1 using immunohistochemical techniques. The tumor response in the injected lesion and in distant metastasis will be monitored. A dose escalation scheme with half-log increments will be used to determine the MTD. The starting dose used was 0.001 micro g/kg and patients are currently being treated at the 0.1 micro g/kg dose level. The MTD of IL-1 alpha has not been determined to date. Patients treated with intralesional IL-1 alpha experienced similar toxicities to those observed with intravenous IL-1 alpha. Biopsy specimens of lesions injected with IL-1 show evidence of vasculitis with lymphoid aggregates surrounding vessels outside the injected tumor nodule and occasionally vessels within the tumor itself. Tumor biopsies have shown evidence of intratumoral lymphoid aggregates that were not identified on pretherapy biopsy specimens. Neither local nor systemic antitumor responses have occurred in this initial group of 15 patients.