The combination of melphalan with prednisolone. Anti-tumor effect and normal tissue toxicity in laboratory systems

The effect of prednisolone upon the therapeutic index of melphalan has been studied in a variety of laboratory systems. The anti-tumour action of melphalan was assessed for a human melanoma xenograft growing in immune-deprived mice, clonogenic cell survival and tumour growth delay being used as end-points. Normal tissue toxicity was assessed for human bone marrow colony-forming units, murine bone marrow colony-forming units, murine gastrointestinal crypt microcolony-forming cells, and mouse survival. Prednisolone had no anti-tumour effect when given alone, but increased the anti-tumour effect of melphalan significantly. No increase in the toxicity of melphalan to marrow or gut colony-forming cells could be demonstrated. However, mouse survival was significantly lower after treatment with the combination than with melphalan alone. This study supports the view that steroids may enhance the anti-tumour effect of some alkylating agents, but this may be at the expense of increased normal tissue toxicity in some circumstances.