Dose‐survival curves of cis‐platinum, melphalan, and velban in human granulocyte/macrophage progenitor cells

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Abstract
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 gran-ulocyte/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) > 10 μg/ml, (b) 0.9 μg/ml, and 1.2 μ/ml, respectively. The respective values for continuous exposure were 0.3 μg/ml, 0.12 μg/ml, and 0.001 μg/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.