Antitumor activity and minimal toxicity of concentrated thymidine infused in nude mice

To avoid infusing large volumes of fluid while treating patients with the standard thymidine solution (30 g/liter), it may be possible to administer this drug in more concentrated form. At 25 degrees C, thymidine is saturating at a concentration of 52 g/liter of 0.6% NaCl solution, and the thymidine concentration at saturation increases with temperature. Nude mice were infused at 29 degrees C with thymidine (60 or 72 g/liter) in cycles consisting of 4 to 5 days infusion followed by 9 days rest. Therapeutically effective doses of concentrated thymidine did not cause significant mortality in mice, and weight loss attributable to treatment was small and reversible. Significant growth inhibition of CA 1 human melanoma heterotransplants was observed after 3 treatment cycles. After 4 or 5 cycles, tumor responses were obtained in 7 mice (6 complete responses) of 12 inoculated with this tumor. These results show that concentrated thymidine solutions are highly effective against human tumor heterotransplants in nude mice and suggest that clinical use of concentrated thymidine may allow practical administration of maximum tolerated doses of this drug.