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.
Similar content being viewed by others
References
Azzoni, P., 1978, The use of gangliosides in the prevention of vincristine neurotoxicity. Il Policlinico, 85, 1–7.
Dantona, A., Labianca, R., and Tabiadon, D., 1978, The use of gangliosides in the prevention and treatment of peripheral neuropathy induced by antitumoral drugs. Proceedings of the International Symposium on Peripheral Neuropathies. Ricerca Scientifica ed Educazione Permanente, 9, 155–158.
Hellmann, K., Hutchinson, G. E., and Henry, K., 1986, Reduction of vincristine toxicity by Cronassial (submitted for publication).
James, S. E., and Salsbury, A. J., 1974, Effect of (±)-1,2-bis(3,5-dioxopiperazin-1-yl) propane on tumour blood vessels and its relationship to the antimetastatic effect in the Lewis lung carcinoma. Cancer Research, 34, 839–842.
Rapport, M. M., and Gorio, A., 1981, Gangliosides in Neurological and Neuromuscular Function, Development and Repair (New York: Raven Press).
Svennerholm, L., 1963, Chromatographic separation of human brain gangliosides. Journal of Neurochemistry, 10, 613–623.
Wallace, R. E., Murdock, K. C., Angier, R. B., and Durr, F. E., 1979, Activity of a novel anthracenedione, 1,4-dihydroxy-5,8-bis[[[2-((2-hydroxyethyl)amino)ethyl] amino]] -9,10-anthracenedione dihydrochloride, against experimental tumours in mice. Cancer Research, 39, 1570–1574.
Wang, G., Finch, M. D., Trevan, D., and Hellmann, K., 1981, Reduction of daunomycin toxicity by razoxane. British Journal of Cancer, 43, 871.
Wexler, H., 1966, Accurate identification of experimental pulmonary metastases. Journal of the National Cancer Institute, 36, 641–643.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hellmann, G., Hutchinson, G.E. & Henry, K. Effect of high dose mitozantrone with Cronassial on the Lewis lung carcinoma and L1210 leukaemia. Clin Exp Metast 5, 157–163 (1987). https://doi.org/10.1007/BF00058061
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00058061