Combination chemotherapy with a new anthracycline glycoside, aclacinomycin-A, and active drugs for malignant lymphomas in P388 mouse leukemia system.

Abstract

Aclacinomycin-A is a new anthracycline glycoside and has less cardiotoxicity than adriamycin. In an attempt to provide an experimental model of a phase III study of aclacinomycin-A, particularly for the treatment of malignant lymphomas, various therapeutic designs of combinations of this drug with other conventional agents were investigated using a P388 mouse leukemia system. Aclacinomycin-A showed no treatment schedule dependency in this tumor system and the optimal dosage of this drug was twice higher than that of adriamycin on each treatment schedule; i.e., single treatment on day 1, three treatments on days 1, 5, and 9, or 10 treatments on every other day from days 1 to 19 after an inoculation of 10(6) leukemic cells on day 0. This antibiotic was ineffective against an adriamycin-resistant subline of P388 leukemia. Among combinations of aclacinomycin-A with cyclophosphamide, vincristine, procarbazine, or bleomycin, the combinations of aclacinomycin-A with cyclophosphamide or vincristine showed a therapeutic synergism in P388 leukemia system.