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In C57B1/6 mice bearing the intramuscular Lewis lung carcinoma, single intravenous doses of Adriamycin showed an higher antineoplastic effectiveness on the primary tumor and its lung metastasis than equal doses of its analog Daunomycin. The in vitro cell-binding of Daunomycin to these tumor cells was higher than that of Adriamycin, but no differences in cytotoxicity were found between the two agents. Pharmacokinetic studies revealed that Adriamycin (and/or its metabolites) accumulated in the neoplastic tissue more promptly, in significantly greater quantities and for longer periods than Daunomycin. The possible importance of these findings in explaining the greater therapeutic activity of Adriamycin in experimental animals is discussed.

The in vitro capacity to take up adriamycin (AM) of murine Lewis lung carcinoma (3LL) cells, derived either from intramuscularly (i.m.) implanted tumor or from its lung metastases, was investigated together with the response of these 2 cell populations to AM treatment. Cell suspensions obtained by mechanical disgregation from primary and secondary tumors directly excised from tumor bearing mice, and primary cultures of these 2 cell populations were exposed to AM in 2 treatment conditions: a higher dose for a short time and a low dose for a longer time. No differences were observed in drug uptake, measured as binding to the cells between primary and metastatic tumor in both experimental conditions. However in the same treatment conditions on the same cell lines AM caused consistently greater cytotoxic effect on pulmonary 3LL metastases than on i.m. primary tumor cells. These findings suggest that the different responses observed may be due to differences on the intrinsic sensitivity of primary and secondary tumor cell populations to AM.

The chemotherapeutic effects of different doses of adriamycin in (C3H x 020)F1 mice bearing mammary carcinoma have been investigated and a model of the growth of neoplastic cells under the influence of treatment is described. An estimate of cell kill and of the fraction of cells surviving after treatment is given by the efficacy constant K, which is a function of the dose level of the drug. The therapeutic value of each treatment is, however, also related to the degree of toxicity which in our model is expressed by the probability of death for each dose level.