Perez-Soler R, Khokhar A R, Lopez-Berestein G
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Hospital and Tumor Institute at Houston 77030.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6462-6.
cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +-(II) (NDDP) was encapsulated in multilamellar vesicles composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a 7:3 molar ratio. Compared with cisplatin, i.v. administration of an equimolar dose of liposome-encapsulated NDDP (L-NDDP) resulted in 15-fold higher peak platinum levels in the spleen (204.7 versus 13.3 micrograms/g dry tissue), 5-fold higher in the lungs (116.4 versus 21.0 micrograms/g dry tissue), 3-fold higher in the liver (71.6 versus 23.9 micrograms/g dry tissue), and 4-fold higher in the blood (14.8 versus 3.9 micrograms/ml). At the optimal dose and schedule, L-NDDP administered i.p. in mice bearing peritoneal L1210 leukemia resulted in the percentage of median survival time of treated mice divided by median survival time of control mice (%T/C) of 312 versus 225 for cisplatin and free NDDP. When administered i.v., L-NDDP was also more active than cisplatin against L1210 leukemia inoculated i.v. (%T/C 186 versus 142). L-NDDP was markedly active against L1210 leukemia resistant to cisplatin (%T/C, 200 versus 112 for cisplatin). In mice bearing liver metastases of M5076 reticulosarcoma, L-NDDP was significatnly more effective than cisplatin at equimolar doses (mean survival time, 57 +/- 9 (SD) days for L-NDDP versus 42 +/- 3 days for cisplatin, P less than 0.05). L-NDDP was also effective in preventing liver metastases of M5076 when administered up to 24 h prior to tumor inoculation (mean survival, 28 +/- 2 days for L-NDDP versus 22 +/- 2 days for cisplatin, P less than 0.05). L-NDDP is significantly non-cross-resistant with cisplatin and more effective against phagocytic and nonphagocytic murine tumors.
顺式 - 双 - 新癸酸根 - 反式 - R,R - 1,2 - 二氨基环己烷铂（II）（NDDP）被包裹在由二肉豆蔻酰磷脂酰胆碱和二肉豆蔻酰磷脂酰甘油以7:3摩尔比组成的多层囊泡中。与顺铂相比，静脉注射等摩尔剂量的脂质体包裹的NDDP（L - NDDP）后，脾脏中的铂峰值水平高15倍（204.7对13.3微克/克干组织），肺中高5倍（116.4对21.0微克/克干组织），肝脏中高3倍（71.6对23.9微克/克干组织），血液中高4倍（14.8对3.9微克/毫升）。在最佳剂量和给药方案下，对患有腹膜L1210白血病的小鼠腹腔注射L - NDDP，治疗小鼠的中位生存时间百分比除以对照小鼠的中位生存时间（%T/C）为312，而顺铂和游离NDDP分别为225。静脉注射时，L - NDDP对静脉接种的L1210白血病也比顺铂更具活性（%T/C为186对142）。L - NDDP对顺铂耐药的L1210白血病具有显著活性（%T/C，顺铂为200对112）。在患有M5076网状细胞肉瘤肝转移的小鼠中，等摩尔剂量的L - NDDP比顺铂显著更有效（平均生存时间，L - NDDP为57±9（标准差）天，顺铂为42±3天，P<0.05）。在肿瘤接种前长达24小时给药时，L - NDDP在预防M5076肝转移方面也有效（平均生存时间，L - NDDP为28±2天，顺铂为22±2天，P<0.05）。L - NDDP与顺铂显著无交叉耐药性，对吞噬性和非吞噬性小鼠肿瘤更有效。
