TY - JOUR
T1 - Protocols for the treatment of human tumor xenografts with camptothecins
AU - Giovanella, B. C.
AU - Natelson, E.
AU - Harris, N.
AU - Vardeman, D.
AU - Stehlin, J. S.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1749-6632.1996.tb26387.x
DO - 10.1111/j.1749-6632.1996.tb26387.x
M3 - Article
C2 - 8993511
AN - SCOPUS:0030467156
SN - 0077-8923
VL - 803
SP - 181
EP - 187
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -