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此前已被证明可以激活 恶性黑色素瘤患者的单核细胞， 手术 本方案的目的是测试三种不同剂量的 重组IFN-γ在转移性疾病（高肿瘤）患者中的应用 负担），看看有一个最佳的免疫调节剂量，在这些 患者 我们在这项研究中招募了18名患者，并在每个治疗组治疗了5名患者。 以下三个剂量水平：0.01 mg/m2 sq、0.1 mg/m2 sq和0.25 mg/m2 sq。 总体而言，治疗耐受性良好，毒性轻微。 串行 血液采样的单核细胞活化的证据表明，这两个 较高剂量产生单核细胞活化的一致增加。 统计学分析表明，这两个之间没有显着差异 剂量，没有证据表明0.1 mg/m2剂量具有任何优效性 超过0.25 mg/m2的剂量。 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）可以有显著的单核细胞 IFN-γ诱导的活化。 与我们之前的研究相比， 肿瘤负荷相对较低的患者，目前的研究没有显示 0.1 mg/m2 sq剂量优于0.25 mg/m2 sq剂量。 因为0.25 mg/m2剂量的IFN-γ已经在II期研究中进行了研究， 在转移性恶性黑色素瘤患者中进行的研究， 答复率低，我们没有进一步调查 0.1 mg/m2 IFN-γ对转移性肝癌患者的有效性 黑素瘤