Failure to alter the course of acute myelogenous leukemia in the rat with subcutaneous deferoxamine.
Deferoxamine (DFO) is an iron chelator that is known to inhibit acute non-lymphocytic leukemia cells in vitro. To explore the possibility that this drug has cytotoxic activity in vivo, rats were inoculated with a small lethal dose (10(2] of tumor cells from the transplantable BN acute myelogenous leukemia model. Animals were then treated with one of several regimens of bolus subcutaneous DFO: 10 mg/day x 5; 20 mg/day x 5; 10 mg/day x approximately 5 weeks; or no DFO. There were no consistently significant differences in survival between any of the DFO and untreated groups. Because the short plasma half-life of DFO was thought to be a potential reason for this lack of protection, a high molecular weight polymeric conjugate of DFO that is known to provide sustained intravascular drug levels was also studied. However, hydroxyethyl starch conjugated with DFO in amounts equivalent to 100 mg free drug (intraperitoneally for 5 days) also failed to have major impact on survival. These findings suggest that it may not be possible to achieve levels of this chelating agent in vivo that are cytotoxic for this disease.
Blatt
J
J
Department of Pediatrics, Children's Hospital of Pittsburgh, PA 15213.
Boegel
F
F
Hedlund
B E
BE
Arena
V C
VC
Shadduck
R K
RK
D000818:Animals; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007279:Injections, Subcutaneous; D007942:Leukemia, Experimental / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains
D003676:Deferoxamine