Effect of administration schedule on the levan-cyclophosphamide combined treatment of Lewis lung carcinoma

Combined treatment with levan and cyclophosphamide (CY) was applied intratumorally to Lewis lung carcinoma tumors in C57B1 mice on day 5 after tumor cell inoculation. Although on that day levan alone had no effect and CY alone caused only temporary regression of tumors, the combined CY-levan treatment caused 60% cure. Levan given before CY was almost as effective as simultaneous administration of both drugs on day 5. Delaying the administration of levan after CY treatment reduced the therapeutic effect. It is concluded that timing in relation to tumor cell inoculation as well as the order of administration of drugs, determine the degree of therapeutic efficacy. In tumor chemo-immunotherapy the final effect is probably due not only to the anti-tumoral effect per se of each drug, but also to the fact that the two agents have an effect on the immune system. Since the immune response may change during tumor development, the effect of timing of administration of an immunomodulator and certainly to two immunomodulators, can be crucial.