Autologous bone marrow grafts in dogs treated with lethal doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.
Hematological and immunosuppressive effects of various single doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were evaluated in the preclinical canine model. Immune function appeared not to be impaired by treatment with CCNU, but severe myelotoxicity contributed to the death of 3 of 4 dogs given 10 mg CCNU per kg and 5 of 5 dogs given 15 mg CCNU per kg within 10 days after drug administration. Infusions of autologous bone marrow protected 6 of 6 dogs receiving 15 mg CCNU per kg and 6 of 6 dogs receiving 20 mg CCNU per kg from lethal marrow failure. Dogs given 30 mg CCNU per kg and autologous marrow died within 7 days from severe gastrointestinal toxicity. We conclude that autologous bone marrow support may allow the use of high-dose CCNU regimens and thereby increase its therapeutic efficacy in the treatment of advanced cancer.
D000818:Animals; D001500:BCG Vaccine; D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation; D004285:Dogs; D004912:Erythrocytes / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D008130:Lomustine / Q000008:administration & dosage / Q000633:toxicity*; D009163:Mycobacterium bovis / Q000276:immunology; D009607:Nitrosourea Compounds / Q000633:toxicity*; D012882:Skin Tests; D013997:Time Factors; D014182:Transplantation, Autologous
D001500:BCG Vaccine; D009607:Nitrosourea Compounds; D008130:Lomustine