Dose-survival curves of cis-platinum, melphalan, and velban in human granulocyte/macrophage progenitor cells.
To optimize the in vitro concentrations of anticancer agents with clinical dose-limiting myelosuppression in the human tumor stem cell assay, we established dose-survival curves for cis-platinum, melphalan, and velban in normal human granulocyte/macrophage colony-forming units (CFU-gm) in a bilayer agar system. The LD50 (drug concentration capable of killing 50% of CFU-gm) of cis-platinum, melphalan, and velban for one-hour exposure was (a) greater than 10 micrograms/ml, (b) 0.9 microgram/ml, and 1.2 micrograms/ml, respectively. The respective values for continuous exposure were 0.3 microgram/ml, 0.12 microgram/ml, and 0.001 microgram/ml. The use of dose ranges based on bone marrow tolerance may influence the clinical value of in vitro tumor sensitivity studies of drugs with hematologic toxicity.
D000970:Antineoplastic Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008558:Melphalan / Q000633:toxicity*; D014747:Vinblastine / Q000633:toxicity*
D000970:Antineoplastic Agents; D014747:Vinblastine; D002945:Cisplatin; D008558:Melphalan