Misonidazole enhancement of the action of BCNU and melphalan against human melanoma xenografts.

We investigated the effects of combinations of BCNU and misonidazole, and melphalan and misonidazole on growth delay in two human malignant melanoma xenograft lines grown in immune-deprived mice. Misonidazole on its own had no effect on the growth of these tumors, but combinations of BCNU-misonidazole and melphalan-misonidazole produced greater tumor growth delays than those produced by the cytotoxic drugs alone. This was accompanied by increased weight loss. Misonidazole in combination with melphalan also increases hemopoietic stem cell toxicity, but in the case of BCNU there was no enhancement of bone marrow toxicity at the dose chosen for tumor experiments.