Survival of human bone marrow cells after in vitro treatment with 12 anticancer drugs and implications for tumor drug sensitivity assays

We investigated the responsiveness of human normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) continuously exposed in vitro to 1 of 12 anticancer drugs. All drugs except bleomycin showed a simple negative exponential dosesurvival curve. The in vitro toxicity of drugs in GM-CFUC did not always correlate with the relative myelosuppressive potency observed in vivo. In addition, tumor specimens from 38 patients mainly with ovarian cancer were cultured in a human tumor colony-forming assay and continuously exposed to drugs at low, intermediate, and high concentrations capable of killing 40%, 78%, and 99% of GM-CFUC, respectively. The most active drugs were cis-platinum, velban, 5-fluorouracil, and 5-fluoro-ara-AMP. Dosesurvival curves of bone marrow progenitor cells may serve as an in vitro reference system for selecting appropriate drug concentrations of myelosuppressive drugs in drug-sensitivity assays of human tumors.