Efficacy of piperazinedione prior to bone marrow transplantation: studies in a rat model for human acute myelocytic leukemia.

Abstract

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.

• Authors: A Hagenbeek, A C Martens
• Journal: Cancer treatment reports (Cancer Treat Rep) 1981 Jul-Aug Vol. 65 Issue 7-8 Pg. 575-82 ISSN: 0361-5960 [Print] United States
• PMID: 7018679 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Piperazines
• 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione

Topics

• Animals
• Antibiotics, Antineoplastic (therapeutic use, toxicity)
• Bone Marrow Transplantation
• Drug Administration Schedule
• Erythrocyte Count
• Injections, Intravenous
• Leukemia, Experimental (therapy)
• Leukemia, Myeloid, Acute (mortality, therapy)
• Leukocyte Count
• Piperazines (therapeutic use, toxicity)
• Platelet Count
• Rats
• Rats, Inbred Strains
• Reticulocytes