Caffeine modulates the antitumor activity and toxic side effects of adriamycin.

To improve both the survival and the response rate of patients, it is necessary to find modifiers which enhance the effects of known anticancer agents. In this study, we examined the effects of caffeine on the antitumor activity and side effects of antitumor agents, using CDF1 male mice. The combination of caffeine with adriamycin significantly enhanced the antitumor activity of adriamycin, by 1.5-fold and 1.9-fold in single- and multi-administration schedules, respectively, compared to the activity of adriamycin only. However, the combination of caffeine with cisplatin had no effect on the antitumor activity of cisplatin in either administration schedule. We examined two biochemical parameters, lipid peroxide level and glutathione peroxidase activity, as indices of adriamycin-induced side effects. The caffeine combination did not enhance the adriamycin-induced changes in these two parameters. Regarding the lethal effect of adriamycin, the caffeine combination had no effect in the single administration schedule, but in the multi-administration schedule, it tended to reduce this acute toxicity. These results suggest that the combination of caffeine with adriamycin can significantly increase the in vivo antitumor activity of this agent without increasing its side effects.