Priming reduces the bone marrow toxicity of carboplatin.
A dose of 170 mg/kg of carboplatin is lethal in mice, death occurring through bone marrow failure. This lethality can be avoided by giving the animals 200 mg/kg cyclophosphamide 1 or 2 days before this dose of carboplatin. The improved normal tissue tolerance cannot be explained by altered pharmacokinetics of carboplatin. Increased survival appears to be associated with a more rapid regeneration of the haemopoietic stem cells. Tumour tissue is not protected in the same way and thus a therapeutic gain can be achieved using this protocol.
Gore
M E
ME
Hills
C A
CA
Siddik
Z H
ZH
Sloane
J P
JP
Winkley
A R
AR
Smith
I E
IE
Millar
J L
JL
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D001835:Body Weight; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D016190:Carboplatin; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000633:toxicity*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D003520:Cyclophosphamide; D016190:Carboplatin