Comparative effect of cisplatin, spiroplatin, carboplatin, iproplatin and JM40 in a human myeloid clonogenic assay.

The relative toxicities of cisplatin and its analogs, spiroplatin, carboplatin, iproplatin and JM40, were tested against normal human progenitor myeloid cells (CFU-GM) in a clonogenic assay. Cells obtained from five bone marrows were incubated for 60 min with various drug concentrations and plated. The mean inhibitory concentrations for 50% of the bone marrow colonies (IC50) were 15.6 micrograms/ml for cisplatin, 0.4 micrograms/ml for spiroplatin, 56.3 micrograms/ml for carboplatin, 36.3 micrograms/ml for iproplatin and 179.5 micrograms/ml for JM40. Ratios of the IC50s of the analogs with cisplatin as reference drug closely followed the corresponding ratios of the clinical maximum tolerated doses. This correlation between the CFU-GM assay results and the clinical myelotoxicity suggests that the assay is adequate for predicting myelotoxicity in vitro and selecting in vitro drug concentrations for the human tumor clonogenic assay.