Kleinerman E S, Gano J B, Johnston D A, Benjamin R S, Jaffe N
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Am J Clin Oncol. 1995 Apr;18(2):93-9. doi: 10.1097/00000421-199504000-00001.
Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthesized lipophilic analogue of muramyl dipeptide. MTP-PE encapsulated in liposomes (L-MTP-PE) allows selective delivery to pulmonary macrophages and circulating monocytes. In vivo administration has resulted in tumor regression in mice with B16 melanoma lung and lymph node metastases and a 40% long-term disease-free survival in dogs with osteosarcoma. Phase I studies have demonstrated that the drug is well tolerated. A Phase II trial using L-MTP-PE was undertaken in relapsed osteosarcoma patients to determine whether L-MTP-PE therapy could improve the progression-free interval in this high-risk group of patients. Patients had histologically proven osteosarcoma and pulmonary metastases that had developed during adjuvant chemotherapy or that were present at diagnosis and had persisted despite chemotherapy. Patients were rendered disease free by surgery. L-MTP-PE, 2 mg/m2, was infused over a 1-hour period twice a week for 12 weeks in 12 patients (Group 1). Sixteen patients (Group 2) received 2 mg/m2 L-MTP-PE twice a week for 12 weeks, then once a week for 12 weeks, for a total of 24 weeks of therapy. Progression-free intervals in each group were calculated from the day of surgery to the day of relapse and compared with the progression-free interval of a historical control group (Group 3) treated postoperatively with chemotherapy at M. D. Anderson Cancer Center between 1980 and 1990. Patients who received 24 weeks of L-MTP-PE therapy had a significant prolongation in time to relapse but those who received 12 weeks of therapy did not. The median time to relapse for group 2 patients was 9.0 months compared with 4.5 months for the control group (Group 3). These data suggest that L-MTP-PE deserves further investigation in a more appropriate adjuvant setting. A nationwide randomized Phase III trial is now underway in newly diagnosed osteosarcoma patients in conjunction with the Children's Cancer Study Group and the Pediatric Oncology Group.
胞壁酰三肽磷脂酰乙醇胺（MTP - PE）是一种合成的胞壁酰二肽亲脂类似物。包裹在脂质体中的MTP - PE（L - MTP - PE）能够选择性地递送至肺巨噬细胞和循环单核细胞。体内给药已使患有B16黑色素瘤肺和淋巴结转移的小鼠出现肿瘤消退，并使患有骨肉瘤的犬长期无病生存率达到40%。I期研究表明该药物耐受性良好。一项针对复发骨肉瘤患者的II期试验采用L - MTP - PE，以确定L - MTP - PE治疗能否改善这一高危患者群体的无进展生存期。患者经组织学证实患有骨肉瘤且在辅助化疗期间出现肺转移，或在诊断时即存在肺转移且尽管接受化疗仍持续存在。患者通过手术实现无病状态。12名患者（第1组）接受L - MTP - PE，2 mg/m²，每周两次，每次1小时，共输注12周。16名患者（第2组）接受L - MTP - PE，2 mg/m²，每周两次，共12周，然后每周一次，共12周，总计24周治疗。计算每组从手术日至复发日的无进展生存期，并与1980年至1990年在MD安德森癌症中心接受术后化疗的历史对照组（第3组）的无进展生存期进行比较。接受24周L - MTP - PE治疗的患者复发时间显著延长，但接受12周治疗的患者未出现这种情况。第2组患者的中位复发时间为9.0个月，而对照组（第3组）为4.5个月。这些数据表明L - MTP - PE在更合适的辅助治疗环境中值得进一步研究。一项全国性随机III期试验目前正在新诊断的骨肉瘤患者中与儿童癌症研究组和儿科肿瘤学组联合开展。
