CCI-779 in metastatic melanoma - A phase II trial of the California Cancer Consortium
CCI-779 in metastatic melanoma - A phase II trial of the California Cancer Consortium
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DOI：
10.1002/cncr.21265
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发表时间：
2005-09-01
期刊：
影响因子：
6.2
通讯作者：
Doroshow, JH
中科院分区：
文献类型：
--
作者：
Margolin, K;Longmate, J;Doroshow, JH
背景。 CCI-779 是免疫抑制剂雷帕霉素的类似物，已在临床前模型中证明具有抗黑色素瘤的活性，并在乳腺癌和肾癌患者中显示出临床益处。 CCI-779 间歇性给药时不会产生免疫抑制作用，其毒性也很温和，包括恶心、腹泻、高甘油三酯血症、血小板减少症、乏力和毛囊性皮炎。方法。目前的试验旨在检测转移性黑色素瘤患者在苯海拉明术前用药后静脉注射 250 毫克每周剂量的 CCI-779 后，疾病进展的中位时间是否超过 18 周。具有可测量的疾病、不超过一种先前的转移性疾病化疗方案和正常器官功能的患者符合资格，并且排除中枢神经系统受累、P450诱导或P450抑制药物或高甘油三酯血症的患者。 结果。 33 名患者（21 名男性）接受了治疗，其中 21 名患者之前曾接受过化疗和/或生物制剂治疗晚期疾病。一名患者出现了持续 2 个月的部分缓解。疾病进展的中位时间和总生存期分别为 10 周和 5 个月。毒性轻微，主要是皮肤粘膜毒性（口腔炎、腹泻和皮疹）。高脂血症是累积性的，并通过降脂药物进行治疗。结论。 CCI-779 在黑色素瘤中的活性不足以保证作为单一药物进行进一步测试。
BACKGROUND. CCI-779 is an analog of the immunosuppressive agent, rapamycin, that has demonstrated activity against melanoma in preclinical models and shown clinical benefit in patients with breast and renal carcinoma. CCI-779 is not immunosuppressive when administered on an intermittent schedule, and its toxicity is modest, consisting of nausea, diarrhea, hypertriglyceridemia, thrombocytopenia, asthenia, and follicular dermatitis.METHODS. The current trial was designed to detect a median time to disease progression of > 18 weeks in patients with metastatic melanoma treated with a 250-mg weekly dose of CCI-779 administered intravenously after diphenhydramine premedication. Patients with measurable disease, no more than one previous chemotherapy regimen for metastatic disease, and normal organ function were eligible, and patients with central nervous system involvement, P450-inducing or P450-suppressing drugs, or hypertriglyceridemia were excluded.RESULTS. Thirty-three patients (21 males) were treated, 21 of whom had been treated previously with chemotherapy and/or biologic agents for advanced-stage disease. One patient had a partial response lasting 2 months. The median time to disease progression and overall survival were 10 weeks and 5 months, respectively. Toxicity was mild and predominantly mucocutaneous (stomatitis, diarrhea, and rash). Hyperlipidemia was cumulative and was managed with lipid-lowering agents.CONCLUSIONS. CCI-779 was not sufficiently active in melanoma to warrant further testing as a single agent.