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Tumor-Marrow Index: A Means of Laboratory Evaluation of Antineoplastic Compounds

( Department of Metabolic Chemotherapy, Experimental Therapeutics Research, Lederle Laboratories, American Cyanamid Co., Pearl River, New York)

A tumor-marrow index (TMI) to be used in the laboratory evaluation of anticancer agents has been defined as that dose causing 50 per cent destruction of the marrow/dose causing 80 per cent suppression of tumor growth in the same animal. Eighteen compounds (eleven antifolic acid analogs, six alkylating agents, and one antipurine) were studied, and the doses causing the effects mentioned were estimated. The TMI was used to compare analogs against the same tumor type rather than the TMI's obtained from the same anticancer agent against different tumors. It was found that there was a marked difference between the indexes as obtained with the antifolic acid compounds against the 6C3HED lymphosarcoma and the alkylating agents against the 72j mammary adenocarcinoma. Of the former, all were 2.0 or greater; whereas of the latter, none was significantly greater than 1.0. Dichloromethotrexate was outstanding of the antifolic acid group; the TMI's of the methotrexate derivatives were generally higher than those of the aminopterin analogs. The TMI obtained with 6-mercaptopurine against Sarcoma 180 was less than 1.0.

Received 6/15/61.