EFFICACY OF IMMUNOMODULATING DOSES OF IFN GAMMA IN METASTATIC MELANOMA

免疫调节剂量的 IFN γ 在转移性黑色素瘤中的疗效

• 批准号: 3874540
• 负责人: J W SMITH
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874540
• 关键词: biological response modifiers; dosage; drug adverse effect; human subject; human therapy evaluation; human tissue; immunomodulators; immunotoxicity; interferons; leukocyte activation disorder; melanoma; metastasis; monocyte; neoplasm /cancer immunotherapy

Recombinant interferon (IFN) gamma has previously been shown to activate monocytes in patients with malignant melanoma rendered disease-free with surgery. The purpose of this protocol was to test three different doses of recombinant IFN-gamma in patients with metastatic disease (high tumor burdens) to see is there was an optimal immunomodulatory dose in these patients. We enrolled 18 patients on this study and treated 5 patients at each of the following three dose levels: 0.01 mg/m sq, 0.1 mg/m sq, and 0.25 mg/m sq. In general, therapy was well-tolerated and toxicities were mild. Serial blood sampling for evidence of monocyte activation showed that the two higher doses produced consistent increases in monocyte activation. Statistical analysis revealed no significant differences between these two doses and there was no evidence for any superiority of the 0.1 mg/m sq dose over the 0.25 mg/m sq dose. This study demonstrates that patients with relatively high tumor burdens (patients with metastatic malignant melanoma) can have significant monocyte activation induced by IFN-gamma. In contrast to our previous study, in patients with relatively low tumor burdens, this current study did not show any superiority of the 0.1 mg/m sq dose over the 0.25 mg/m sq dose. Because the 0.25 mg/m sq dose of IFN-gamma has been studied in a phase II study in patients with metastatic malignant melanoma and found to have a low response rate, we did not further pursue investigation of the effectiveness of 0.1 mg/m sq of IFN-gamma in patients with metastatic melanoma.

重组干扰素 (IFN) γ 先前已被证明可以激活 恶性黑色素瘤患者的单核细胞通过 外科手术。 该方案的目的是测试三种不同剂量的 重组IFN-γ治疗转移性疾病患者（高肿瘤 负担）看看这些药物中是否存在最佳免疫调节剂量 患者。 我们在这项研究中招募了 18 名患者，并在每个研究中治疗了 5 名患者。 以下三个剂量水平：0.01 mg/m2、0.1 mg/m2 和 0.25 mg/m2。 一般来说，治疗耐受性良好且毒性轻微。 串行 血液采样以获取单核细胞激活的证据表明，这两种 较高剂量会导致单核细胞活化持续增加。 统计分析显示两者之间没有显着差异 剂量，没有证据表明 0.1 mg/m2 剂量有任何优越性 超过 0.25 mg/m2 剂量。 这项研究表明，肿瘤负荷相对较高的患者 （转移性恶性黑色素瘤患者）可有明显的单核细胞 IFN-γ诱导的激活。 与我们之前的研究相比，在 肿瘤负荷相对较低的患者，目前的研究并未显示 0.1 mg/m2 剂量相对于 0.25 mg/m2 剂量的任何优越性。 因为 0.25 mg/m2 剂量的 IFN-γ 已在 II 期研究中 对转移性恶性黑色素瘤患者进行的研究发现， 回复率低，我们没有进一步调查 0.1 mg/m2 的 IFN-γ 对转移性患者的有效性 黑色素瘤。