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.

Radiation effects on mouse incisor teeth following whole-body doses of up to 16 gray.

Experiments were performed to determine the threshold dose of radiation above which macroscopic tooth damage in C57BL mice occurs, the sequence of appearance of this damage, and the extent and rate of recovery in relation to radiation dose. Protection from the acute effects of radiation doses well in excess of the LD90 was obtained by the administration of non-absorbable antibiotics and bone marrow reconstitution, without the use of radioprotective drugs. However, gross effects on the incisors were observed at doses in excess of 10 gy. Body weight changes were to some extent linked with the incidence of tooth damage.

Effect of high-dose melphalan on marrow and intestinal epithelium in mice pretreated with cyclophosphamide.

The lethal effect of high-dose melphalan in mice could be offset by pretreatment with cyclophosphamide, cytosine arabinoside or low-dose melphalan. The reason for improved survival is unclear. Althoug animals given high-dose melphalan died with symptoms of gut death, in only one instance, that with low-dose melphalan itself, did pretreatment protect the intestinal epithelium as measured by the microcolony assay. A small enhancement in the recovery of the haemopoietic tissue in pretreated animals was noted, although this on its own is unlikely to explain the phenomenon. Experiments in tumour-bearing mice showed that pretreatment with cyclophosphamide did not reduce the toxicity of melphalan to the Lewis lung carcinoma.