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.