Experimental basis for increasing the therapeutic index of carboplatin in brain tumor therapy by pretreatment with WR compounds.
We tested an experimental strategy to decrease the dose-limiting hematotoxicity of carboplatin without compromising its activity against brain tumors. The effect of pretreatment with WR-1065, a chemomodifier that penetrates brain poorly, on carboplatin's cytotoxicity was evaluated in human hematopoietic granulocyte-monocyte progenitor cells and in three human glioblastoma cell lines. WR-1065 reduced bone marrow toxicity without decreasing carboplatin's activity against glioblastoma cells. These results suggest that the therapeutic index of carboplatin might be increased in the treatment of malignant brain tumors.
Doz
F
F
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Berens
M E
ME
Spencer
D R
DR
Dougherty
D V
DV
Rosenblum
M L
ML
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D001932:Brain Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008624:Mercaptoethylamines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D008624:Mercaptoethylamines; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D016190:Carboplatin