Pharmaceutical compositions comprising two or more therapeutically active agents such as two or more anticancer agents conjugated to one or more biocompatible polymers wherein the molar ratio of the agents and/or schedules of delivery provide a synergistic therapeutic effect are described. Methods of making and using the pharmaceutical compositions are further described. In one embodiment the pharmaceutical compositions contain topoisomerase I and topoisomerase II inhibitors conjugated to the same or different biocompatible polymers. The two or more anticancer agents are covalently coupled to the polymer(s) and thereby can be delivered to a tumor at a molar ratio which provides a synergistic effect. Optionally the agents are coupled indirectly to the polymer(s) via a linker.
