The effects of adriamycin (AM) and daunorubicin (DM) have been compared in DBA/2 mice bearing an ascitic murine lymphocytic leukemia (P-288). Over a range of doses (either a single dose, or 1 dose daily for 5 days), the i.p. administration of AM increased the average survival times of leukemic mice from about 12 days (controls) to 25 days or more, and 10 to 20% of the animals were long-term survivors. In contrast, DM increased survival time only about 40% or less, with no long-term survivors. Mice given whole-body irradiation (250 R) or cyclophosphamide (150 mg/kg) prior to tumor implantation showed markedly decreased differential responses to these drugs. When AM was administered daily for 5 days, concurrently with methotrexate to mice bearing L1210 or P-288, the increased average survival times due to AM alone were reduced by the drug combination in both tumors.
Tissue concentrations of the agents were determined by fluorometric analysis. Uptake of AM by P-288 in normal and irradiated hosts was generally less than that of DM during the early times after administration, although such differences diminished by 3 to 4 hr and after high doses. There were no marked differences in uptake of AM and DM by liver and thymus; in contrast, DM was found in spleen at concentrations about twice those of AM. These concentrations were reduced when mice were given irradiation and P-288 cells prior to administration of the drugs. The results indicate that DM may be more toxic to the spleen and, therefore, more immunosuppressive than AM. This difference may account for the greater efficacy of AM in various transplanted tumors.
This work was supported by USPHS Core Program Grant CA-13038 from the National Cancer Institute and by an allocation from American Cancer Society Institutional Grant IN-54-L-17 to Roswell Park Memorial Institute.