Premium
Protocols for the Treatment of Human Tumor Xenografts with Camptothecins
Author(s) -
GIOVANELLA B. C.,
NATELSON E.,
HARRIS N.,
VARDEMAN D.,
STEHLIN J. S.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb26387.x
Subject(s) - camptothecin , pharmacology , medicine , biology , biochemistry
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 mammals. 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 camptotecins 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.