Modulation of chemotherapeutic drug activity with polyribonucleotides or with interferon

Mouse interferon, or human hybrid recombinant interferon alpha A/D, administered during the 2 day period following the administration of a toxic dose of 5-fluorouracil (FUra), yielded significant protection from body weight loss, leukopenia, and mortality in Balb/c X DBA/8 F1 mice. Protection against FUra-toxicity also was observed when the interferon inducer polyinosinic-polycytidylic acid [poly(I,C)] was administered with FUra. Since it is known that nonproliferating cells exhibit diminished sensitivity to FUra as compared with proliferating cells, it appears likely that the decreased toxicity seen in these experiments can be ascribed to the antiproliferative action of interferon on normal tissues in the mouse which are sensitive to the action of FUra. When poly(I,C) and FUra were coadministered to mice bearing colon tumor 26, the tolerated dose of FUra was increased significantly, and this resulted in significantly increased antitumor activity. These results indicate that differential cytokinetic modulation with interferon, or possibly with other known antiproliferative agents, may provide a new approach for improving clinical results in cancer therapy with available drugs.