The novel highly lipophilic topoisomerase I inhibitor DB67 is effective in the treatment of liver metastases of murine CT-26 colon carcinoma.
Colorectal carcinoma occurs in 1 of 20 individuals in most developed countries. The relapse after resection with metastatic liver disease is a major cause of death. 7-t-Butyldimethylsilyl-10-hydroxycamptothecin (DB67) has been incorporated into liposomes allowing for intravenous (i.v.) administration. A preclinical efficacy study of liposomal DB67 was performed using the colon carcinoma CT-26 cell line. The therapeutic dose for DB67 and liposomal DB67 was found to be 7 mg/kg per day using the qdx5/1 schedule. The results are compared with those obtained with irinotecan. The treatment with liposomal DB67 administered intravenously was more effective in reducing the weight and volume of primary spleen tumors and the weight and extent of liver metastases than free DB67 or liposomal DB67 administered intraperitoneally, but less effective than irinotecan. When the primary tumor was resected, treatment with liposomal DB67 administered intravenously was more effective in reducing the weight and extent of liver metastases than DB67 or liposomal DB67 administered intraperitoneally, and irinotecan. DB67 showed a higher accumulation in spleen and liver after its i.v. administration in liposomal form compared with its free or liposomal form administered intraperitoneally. DB67 and liposomal DB67 are more effective than irinotecan in the treatment of liver metastases after resection of the primary tumor.
Lopez-Barcons
Lluis A
LA
Department of Medicine and Molecular Pharmacology, Albert Einstein Cancer Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Zhang
Junhong
J
Siriwitayawan
Gunching
G
Burke
Thomas G
TG
Perez-Soler
Roman
R
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D000077146:Irinotecan; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000556:secondary*; D051379:Mice; D017646:Organosilicon Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013156:Splenectomy; D014018:Tissue Distribution; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D008081:Liposomes; D017646:Organosilicon Compounds; D059004:Topoisomerase I Inhibitors; C415575:7-tert-butyldimethylsilyl-10-hydroxycamptothecin; D000077146:Irinotecan; D002166:Camptothecin