The effect of cytotoxic drugs with or without misonidazole on leucopenia in three strains of mice.

Leucopenia is a major dose-limiting effect of many cytotoxic drugs. We have measured the effect of melphalan and four other drugs either alone, or with misonidazole on total white cell count in mice. Three strains were used, though not with all drugs. White cell counts were determined 3, 5, and 7 days after giving the cytotoxic drugs either with or without misonidazole. For all the drugs used, the nadir in white cell count was at 3 to 5 days when the dose-effect curves were approximately expotential. Only in the case of chlorambucil and mitomycin-C did misonidazole enhance the leucopenia. There was no enhancement of the effects of melphalan, cyclophosphamide or CCNU. In the case of mitomycin C the effect of misonidazole was to delay the recovery in the white cell count. It would appear that enhanced leucopenia from the combination of misonidazole with cytotoxic drugs may depend on the drug used. With three of the five drugs, the absence of an effect of misonidazole implies that any enhanced damage to tumors would represent a true increase in therapeutic effectiveness.