Abstract: Maleimide and succinimide derivatives were found to be effective topoisomerase II catalytic inhibitors. Due to this property, the maleimide and succinimide derivatives were investigated for their use as cytostatic agents and thus in the treatment of cancer. The compounds of the invention can be used in combination treatments with other cytostatic agents, such as topoisomerase II poisons. The maleimide and succinimide derivatives, due to their effective topoisomerase II catalytic inhibitory activity, are also useful as extravasation agents, such as upon administration of a topoisomerase II poison.

Abstract: The present invention relates to a method for selectively killing tumor or metastatic cells within a defined compartment of the organism of a large mammal, in particular a human, said method comprising administering to a mammal an effective tumor—or metastasis-killing amount of a topoisomerase II poison except doxorubicin, and protecting non-tumorous tissue of the mammal against the toxic action of the topoisomerase II poison by administration of a bis-dioxypiperazine compound. In particular, the invention relates to a pharmaceutical kit for selectively killing tumor or metastatic cells within the central nervous system in a large mammal, in particular a human, said kit comprising: a) a dosage unit of a bis-dioxypiperazine and a pharmaceutically acceptable carrier, and b) a dosage unit of topoisomerase II poisons except doxorubicin and a pharmaceutically acceptable carrier.