Abstract
A method is outlined for the quantitative comparison of active antitumor compounds. This method has been applied to studies with the 6C3HED Iymphosarcoma in C3H mice. It is possible to obtain three types of information from a dose-response experiment: 1) the relationship of drug dosage to tumor inhibition; 2) the relationship of dosage to toxicity; and 3) the relationship of toxicity (weight loss) to tumor inhibition. From these relationships a "carcinostatic index" for a compound can be calculated by dividing the toxic dose by the effective dose. A high index indicates selective antineoplastic activity. The relationship of the dose-response curve, the toxicity-response curve and the dosetoxicity curve to the carcinostatic index is discussed. The carcinostatic index is found to have a coefficient of variation of 36%. Nine folic acid antagonists arecompared. On the basis of the carcinostatic index, chloromethotrexate, dichloromethotrexate and 4-amino-9, 10-dimethylpterolglutamic acid are the most effective agents against the present test system. These results indicate that it is possible to vary the chemical structure of an anticancer compound in such a way as to make the compound more effective in tumor inhibition and less toxic toward the host. It is emphasized that the antitumor potency of a compound is not the sole criterion of its effectiveness. Miscellaneous types of compounds studied appear less favorable against the 6C3HED lymphosarcoma than the folic acid antagonists. It is concluded that the carcinostatic index appears to be a useful indicator of the relative merits of anticancer compounds.
Footnotes
- Received September 28, 1959.
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