Efficacy of piperazinedione prior to bone marrow transplantation: studies in a rat model for human acute myelocytic leukemia.
The efficacy and toxicity of piperazinedione were investigated in a Brown Norway rat model for acute myelocytic leukemia (BNML). Treatment was started at a stage which is comparable to a "full-blown" relapse in human patients. Early toxicity-induced deaths due to the very strong myelosuppressive effect of the drug could be prevented by bone marrow transplantation followed by repeated blood transfusions. However, with a total dose of 16 mg/kg (human dose, 85 mg/m2), death caused by GI tract and lung damage was inevitable. As judged by prolongation of survival, at the most of a 9-log cell-kill was achieved. No cures were obtained, since the total tumor load at the start of treatment was greater than 10(9) cells (about 5 X 10(9)). The possible presence of drug-resistant cells was not excluded. No significant differences in efficacy were found between daily "push" treatment and split daily doses using total doses of 10-12 mg/kg.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D016026:Bone Marrow Transplantation; D004334:Drug Administration Schedule; D004906:Erythrocyte Count; D007275:Injections, Intravenous; D007942:Leukemia, Experimental / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D007958:Leukocyte Count; D010879:Piperazines / Q000627:therapeutic use* / Q000633:toxicity; D010976:Platelet Count; D051381:Rats; D011919:Rats, Inbred Strains; D012156:Reticulocytes
D000903:Antibiotics, Antineoplastic; D010879:Piperazines; C003905:3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione