Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia

Mice given mitozantrone (MTZ) in doses close to the LD100 (high dose, HD) all survive if they also receive at the same time a mixture of four defined gangliosides--Cronassial (CRN). The protective action of CRN against the toxic effects of MTZ is not accompanied by a reduction of the antitumour activity of MTZ; on the contrary the reduced toxicity permits higher doses of MTZ to be given with the result that better antitumour activity can be achieved. This is illustrated by the highly effective action of MTZ and CRN in preventing the appearance of Lewis lung carcinoma (3LL) metastases, a tumour against which MTZ when used alone is inactive even at maximum tolerated doses (MTD). However, the effect of the combination on the primary 3LL is less pronounced. HD-MTZ and CRN are also more effective than MTD-MTZ alone in preventing dissemination and proliferation of L1210 leukaemia. Although the mechanism of the CRN protective effect is as yet unclear it appears that CRN prevents the lethal effects of necrotizing enteritis produced by HD-MTZ. It is concluded that CRN by reducing MTZ toxicity without interfering with its activity increases the therapeutic index of MTZ and permits an expanded exploration of its dose response curve against a variety of malignancies.