Disposition of [3H]actinomycin D in tumor-bearing mice

A single, nonlethal dose of actinomycin D will cause total regression and cure of Ridgway osteogenic sarcoma in mice. A cure is not obtained with a single dose daily for 7 days, a dose regimen which kills 10% of normal C57BL/6 X DBA/2 mice. This suggests that actinomycin D is more effective on a single high-dose schedule than on chronic daily therapy. Analysis of drug exposure in Ridgway osteogenic sarcoma and normal mouse tissues following the single and multiple-dose regimens suggests the difference in therapeutic response is due to drug exposure at a higher concentration in Ridgway osteogenic sarcoma after the single high dose than after the multiple-dose regimen. This may be related to the higher drug concentration attained in blood following the single-dose regimen than is attained with the multidose regimen.