Thirty-five human tumors of various histological types xenografted at various sites into nude mice and rats have been used to assess the anticancer activity of camptothecin and derivatives administered by different routes (subcutaneous, intramuscular, intravenous, intrastomach, and transdermal). Camptothecins are active against human tumors at every site including the brain. So far, the best anticancer/toxicity ratio has been found with 9-nitrocamptothecin (9NC) and 9-aminocamptothecin (9AC) to which 9NC converts in the body of mammal. Comparing the results obtained during clinical trials with the animal ones, it is evident that camptothecins are much less active in humans than in mice against human tumors. This is probably due to the fact that in humans the lactone ring of camptothecins opens much faster than in mice. Measurement of the area under the curve (AUC) in mice and humans under comparable conditions of administration gives values of 3% closed lactone for man versus 55% in mice for 9NC. Clearly this is the crucial problem to overcome in order to improve the efficacy of the camptothecins as anticancer agents.
|Original language||English (US)|
|Number of pages||7|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science