Treatment and prophylaxis of experimental liver metastases of M5076 reticulosarcoma with cis-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 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.
Perez-Soler
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R
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Hospital and Tumor Institute at Houston 77030.
Khokhar
A R
AR
Lopez-Berestein
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G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002460:Cell Line; D007939:Leukemia L1210 / Q000188:drug therapy; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary* / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000517:prevention & control / Q000556:secondary* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II)