Treatment and prophylaxis of experimental liver metastases of M5076 reticulosarcoma with m-bis-neodecanoato-trans-R, R-1, 2-diaminocyclohexaneplatinum(II) encapsulated in multilamellar vesicles

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 73 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 133 μg/g dry tissue), 5-fold higher in the lungs (116.4 versus 21.0 Mg/g dry tissue), 3-fold higher in the liver (71.6 versus 23.9 μgg dry tissue), and 4-fold higher in the blood (14.8 versus 3.9 μg/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 significantly more effective than cisplatin at equimolar doses (mean survival time, 57 ± 9 (SD) days for L-NDDP versus 42 ± 3 days for cisplatin, P< 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 < 0.05). L-Nddp is significantly non-cross-resistant with cisplatin and more effective against phagocytic and nonphagocytic murine tumors.