INTERFERON-ALFA WITH OR WITHOUT INDOMETHACIN IN MELANOMA

本研究是一项前瞻性随机试验， 给予或不给予吲哚美辛的患者 恶性黑色素瘤，以确定什么样的影响，如果有的话，吲哚美辛 可能具有毒性、免疫调节和治疗活性 干扰素的作用 53例患者 根据体能状态分层，并随机分配至 接受干扰素α-2b 2000万单位/m2静脉注射5 每周30天，持续四周，随后为1000万单位/m2 皮下注射，每周三次，无论是否 吲哚美辛25毫克，口服，每日三次。 总体主要 应答率为13%（3名完全应答者和3名部分应答者 47例可评估患者中的应答者），并且两组均相等。 吲哚美辛对自然杀伤细胞活性没有影响， 外周血中2 ′-5 ′寡腺苷酸合成酶诱导 单核细胞 平均最大温升 由干扰素显著降低（从102.1至100.7，p = 0.001）。 0.017），但发病率和严重程度 干扰素相关的疲劳，性能状态下降， 肝功能检查升高，骨髓抑制，头痛， 抑郁症，和混乱是没有什么不同的任何一个手臂， study. 吲哚美辛并不能减少干扰素的使用频率 剂量减少的毒副作用，并没有让 给予更高剂量的干扰素。 我们的结论是 吲哚美辛可以减轻干扰素引起的发热 用干扰素治疗恶性黑色素瘤患者 而不降低治疗或免疫调节活性 这个代理人。 因为发烧很少是剂量限制性毒性 然而，吲哚美辛对这种干扰素的作用微乎其微。 接受本研究所述剂量干扰素治疗的患者。

This study was a prospective randomized trial of interferon alfa given either with or without indomethacin in patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory and therapeutic activity of interferon in this disease. Fifty-three patients were stratified according to performance status and randomized to receive interferon alfa-2b 20 million units/m2 intravenously five days per week for four weeks followed by 10 million units/m2 subcutaneously three times per week either with or without indomethacin 25 mg po three times a day. The overall major response rate was 13 percent (3 complete responders and 3 partial responders among 47 evaluable patients) and was equal on both arms. Indomethacin had no effect on natural killer cell activity or induction of 2'-5' oligoadenylate synthetase in peripheral blood mononuclear cells. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, p = 0.017) by indomethacin, but the incidence and severity of interferon-related fatigue, performance status reductions, elevations in liver function tests, myelosuppression, headache, depression, and confusion was no different on either arm of the study. Indomethacin did not reduce the frequency of interferon dose reductions for toxic side effects and did not allow the administration of higher interferon doses. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma treated with interferon without a reduction in the therapeutic or immunomodulatory activity of this agent. Because fever is rarely the dose limiting toxicity of interferon, however, indomethacin is of marginal benefit to such patients receiving interferon in the doses outlined in this study.