PHASE 1 EVALUATION OF INTRATUMORAL INTERLEUKIN-1 ALPHA

该方案的目的是确定最大耐受剂量 (MTD)肿瘤内白介素I(IL-1)α。我们计划检查 瘤内注射IL-1前后的肿瘤标本 使用免疫组织化学技术。注射中的肿瘤反应 将监测病变和远处转移的情况。 将使用半对数增量的剂量递增方案 确定MTD。起始剂量为0.001 mU·g/kg；患者为 目前正在以0.1mU-g/kg剂量水平治疗。MTD还没有 到目前为止已经确定了。 接受肿瘤内IL-1α治疗的患者经历了类似的 对静脉注射IL-1α观察到的毒性。活组织检查 注射IL-1的皮损标本显示血管炎的证据 注射肿瘤结节外血管周围的淋巴样聚集 偶尔也会在肿瘤内部形成血管。肿瘤活组织检查已经 有证据表明肿瘤内有淋巴聚集，而不是 在治疗前的活组织检查样本上被确认。既不是局部的，也不是系统性的 在最初的15名患者中，已经出现了抗肿瘤反应。

The purpose of this protocol is to determine the maximum tolerated dose (MTD) of intralesional interleukin-I (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 metastases will be monitored. A dose escalation scheme with half-log increments will be used to determine the MTD. The starting dose was 0.001 mu-g/kg; patients are currently being treated at the 0.1 mu-g/kg dose level. The MTD 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.