PHASE II TRIAL OF IL-1 ALPHA + INDOMETHACIN IN MELANOMA PATIENTS

IL-1α对人黑色素瘤细胞的抗增殖活性 株系，在体内导致小鼠黑色素瘤肿瘤缩小，可诱导 干扰素和白介素2在黑色素瘤中具有活性，并可以 增强细胞毒T细胞和其他效应细胞的活性。 动物研究表明，吲哚美辛可增强抗肿瘤作用 IL-1的作用。出于这些原因，我们设计了这项第二阶段研究 测定黑色素瘤患者IL-1αPlus的抗肿瘤活性 吲哚美辛使用最大耐受量的IL-1α 早期的第一阶段试验。共有36名患者进入了这项研究， 和32个是可评估的反应。没有患者主要是 内脏转移对治疗有反应。一名患者患有 非内脏转移瘤有部分反应，一名患者有 次要回应。这些结果表明IL-1α水平较低。 黑色素瘤的活动性。为了加强这项活动，我们正在 计划一项将依托泊苷(VP-16)与依托泊苷(VP-16)联合使用的后续临床试验 这种疗法基于临床前研究，已经证明了协同作用。 结合在一起。

IL-1alpha has antiproliferative activity against human melanoma cell lines, causes murine melanoma tumors to shrink in vivo, can induce interferons and interleukin-2 which have activity in melanoma, and can enhance the activity of cytotoxic T cells and other effector cells. Animal studies suggested that indomethacin increased the antitumor effects of IL-1. For these reasons, we designed this phase II study in melanoma patients to determine the anti-tumor activity of IL-1alpha plus indomethacin using the maximum tolerated dose of IL-1alpha from our earlier phase I trial. A total of 36 patients have entered the study, and 32 are evaluable for response. No patient with predominately visceral metastases responded to treatment. One patient with non-visceral metastases had a partial response and one patient had a minor response. These results indicate that IL-1alpha has a low level of activity in melanoma. In an effort to enhance this activity, we are planning a follow-up clinical trial that combines etoposide (VP-16) with this regimen based on preclinical studies that have demonstrated synergy of the combination.