MacEwen E G, Kurzman I D, Helfand S, Vail D, London C, Kisseberth W, Rosenthal R C, Fox L E, Keller E T, Obradovich J
Department of Medical Sciences, University of Wisconsin, Madison 53706.
J Drug Target. 1994;2(5):391-6. doi: 10.3109/10611869408996814.
Targeted delivery of macrophage activating agents is an attractive approach to treat micrometastatic disease. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a potent activator of monocytes/macrophages in humans, mice, and dogs. We have conducted clinical trials in dogs with malignant and highly metastatic spontaneous tumors. Presented are results of our trials evaluating L-MTP-PE in combination with surgery and chemotherapy in dogs with spontaneous osteosarcoma and hemangiosarcoma, particularly relevant malignancies having having many similarities to human cancer. Osteosarcoma dogs received chemotherapy following surgery (cisplatin q 28 days x 4). At completion of chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.021). Dogs with splenic hemangiosarcoma received combination chemotherapy following surgery (doxorubicin and cyclophosphamide q 21 days x 4). At the first chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.03). These studies show that L-MTP-PE is an effective agent for treatment of metastasis and can be safely administered in combination with chemotherapy.
靶向递送巨噬细胞激活剂是治疗微转移性疾病的一种有吸引力的方法。脂质体包裹的胞壁酰三肽磷脂酰乙醇胺(L-MTP-PE)是人类、小鼠和犬单核细胞/巨噬细胞的有效激活剂。我们对患有恶性和高转移性自发性肿瘤的犬进行了临床试验。本文展示了我们在患有自发性骨肉瘤和血管肉瘤的犬中评估L-MTP-PE联合手术和化疗的试验结果,这些相关恶性肿瘤与人类癌症有许多相似之处。骨肉瘤犬在手术后接受化疗(顺铂,每28天一次,共4次)。化疗结束后,犬被随机分组接受L-MTP-PE或安慰剂。与安慰剂组相比,L-MTP-PE组的中位生存时间显著更长(p < 0.021)。患有脾脏血管肉瘤的犬在手术后接受联合化疗(阿霉素和环磷酰胺,每21天一次,共4次)。在第一次化疗时,犬被随机分组接受L-MTP-PE或安慰剂。与安慰剂组相比,L-MTP-PE组的中位生存时间显著更长(p < 0.03)。这些研究表明,L-MTP-PE是一种治疗转移的有效药物,可与化疗联合安全给药。