EFFICACY OF IMMUNOMODULATING DOSES OF IFN GAMMA IN METASTATIC MELANOMA

重组干扰素(干扰素)伽马此前已被证明可激活 单核细胞在恶性黑色素瘤患者中的应用 做手术。该方案的目的是测试三种不同剂量的 重组干扰素-γ在转移性疾病(高肿瘤)患者中的应用 负担)，看看这些是否存在最佳免疫调节剂量 病人。 我们在这项研究中招募了18名患者，并分别治疗了5名患者 以下三个剂量水平：0.01 mg/msq、0.1 mg/msq和0.25 mg/msq。 总体而言，治疗耐受性良好，毒性轻微。连载 采血检测单核细胞活化的证据显示，两人 更高的剂量会持续增加单核细胞的激活。 统计分析表明，两者之间没有显著差异 剂量，没有证据表明0.1毫克/平方米的剂量有任何优势 超过0.25毫克/立方米的剂量。 这项研究表明，肿瘤负担相对较高的患者 (转移性恶性黑色素瘤患者)可有显著的单核细胞 干扰素-γ诱导的活化。与我们之前的研究不同，在 肿瘤负担相对较低的患者，目前的研究没有显示 0.1 mg/m sq剂量相对于0.25 mg/m sq剂量的优势。 因为0.25 mg/m平方剂量的干扰素-伽马已经进行了二期研究。 对转移性恶性黑色素瘤患者的研究发现 回应率低，我们没有进一步调查 0.1 mg/msq干扰素治疗转移性肿瘤的疗效观察 黑色素瘤。

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.