Urba W J, Hartmann L C, Longo D L, Steis R G, Smith J W, Kedar I, Creekmore S, Sznol M, Conlon K, Kopp W C
Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Maryland.
Cancer Res. 1990 May 15;50(10):2979-86.
Muramyl tripeptide phosphatidylethanolamine (MTP-PE; CGP 19835A from Ciba Geigy) is a synthetic muramyl tripeptide structurally related to bacterial cell wall constituents. MTP-PE activates monocytes in vitro to a tumoricidal state and has in vivo antitumor effects in animal models. We studied the toxicity and immunomodulatory effects of once weekly i.v. administration of liposomal-encapsulated MTP-PE for 8 weeks in 27 patients with advanced malignancies. Doses ranged from 0.1 to 2.7 mg/m2. No major tumor responses were seen; 11 patients had stable disease after 8 weeks of therapy and 3 continued on maintenance therapy because of minor tumor regressions and/or clinical improvement. MTP-PE at these doses was well tolerated. Shaking chills and fevers were the most common toxicities and occurred at all dose levels. There was no treatment-induced loss of performance status. Immunomodulatory studies revealed evidence of a biological effect on monocytes. C-reactive protein levels rose in the majority of patients with end-of-treatment values 2 to 10 times higher than baseline. Serum neopterin levels were consistently increased 24 h after MTP-PE administration and significant decreases in expression of two different types of Fc receptors on peripheral blood monocytes were noted 6 h after treatment. Although no major tumor responses were seen in this group of patients with advanced malignancies, MTP-PE was well tolerated and exerted biological effects on monocytes. Serum neopterin levels may be a useful marker for the biological effects of MTP-PE.
胞壁酰三肽磷脂酰乙醇胺（MTP - PE；来自汽巴 - 嘉基公司的CGP 19835A）是一种结构上与细菌细胞壁成分相关的合成胞壁酰三肽。MTP - PE在体外可将单核细胞激活至杀肿瘤状态，并且在动物模型中具有体内抗肿瘤作用。我们研究了27例晚期恶性肿瘤患者每周静脉注射脂质体包裹的MTP - PE，持续8周的毒性和免疫调节作用。剂量范围为0.1至2.7mg/m²。未观察到明显的肿瘤反应；11例患者在治疗8周后病情稳定，3例因肿瘤轻度消退和/或临床症状改善而继续接受维持治疗。这些剂量的MTP - PE耐受性良好。寒战和发热是最常见的毒性反应，在所有剂量水平均有发生。未出现因治疗导致的功能状态下降。免疫调节研究显示对单核细胞有生物学效应的证据。大多数患者的C反应蛋白水平升高，治疗结束时的值比基线高2至10倍。MTP - PE给药后24小时血清新蝶呤水平持续升高，治疗后6小时外周血单核细胞上两种不同类型的Fc受体表达显著降低。尽管在这组晚期恶性肿瘤患者中未观察到明显的肿瘤反应，但MTP - PE耐受性良好，并对单核细胞产生生物学效应。血清新蝶呤水平可能是MTP - PE生物学效应的有用标志物。
