Caffeine Enhancement of the Effect of Anticancer Agents on Human Sarcoma Cells

It is necessary to find modifiers which enhance the effects of known anticancer agents in order to improve both survival rate and local curability of patients with high‐grade sarcomas. In this study, the effect of anticancer agents combined with caffeine was examined on cultured sarcoma cells and fresh human sarcoma specimens, utilizing the human tumor clonogenic assay technique. The combination of cisplatin and caffeine showed a synergistic inhibition of the growth of two strains of cultured sarcoma cells tested, and 14 of 18 fresh human sarcoma specimens (77.8%). This synergistic effect of caffeine was also observed with cyclophosphamide (44.8%), mitomycin C (44.8%) and adriamycin (27.8%). The combination of vincristine or methotrexate with caffeine, however, did not exhibit a synergistic effect. Caffeine, therefore, enhanced the effect of four cytotoxic DNA damaging agents. No antag‐ onistic effects were seen in our series. This study suggests that caffeine may be useful in enhancing the tumoricidal effect of anticancer drugs, especially DNA‐damaging agents, and possibly may aid in overcoming natural drug resistance.