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Chemotherapy Studies in an Animal Tumor Spectrum

III. Evaluation of the Toxicity Differential Index¹

Division of Special Studies and Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University Medical College, and Department of Medical Physics, Memorial Hospital for Cancer and Allied Diseases, New York, New York

The efficacy of 14 drugs in the treatment of 8 rodent tumors has been assessed by means of the toxicity differential index (TDI) proposed by Bross and Tarnowski (2). This index provides a numerical value, with confidence limits, for ranking compounds in the order of their relative efficacy within a tumor system. The chemotherapeutic effect of a drug over a wide range of graded doses has been assessed by tumor diameter. With the use of this measure of tumor size, effect could be assayed at intervals during treatment—in this study at 7 days and 14 days after beginning of treatment. The toxicity of the drug for the host has been recorded by the weight loss of the animal. The effect of weight loss per se on tumor diameter has been accounted for by a study of control groups of tumor-bearing animals subjected to various degrees of food restriction.

Most of the 120 tumor-treatment combinations observed showed the linear relationship between tumor diameter and host weight change on which the TDI depends. There was a good degree of reproducibility among triplicate trials for a given combination: a few of the combinations were rejected on the basis of nonparallelism of the lines fitted by least squares. Although this method has broad applicability, some limitations concerning its use have been assessed.

A comparison has been made between evaluations by the TDI and by treated/control (T/C) methods.

¹ This study was supported in part by funds from the Cancer Chemotherapy National Service Center (Contract SA-43-ph-2445), National Cancer Institute, and Division of Research Facilities and Resources (General Research Support Grant 1 SO1 FR-05534), NIH, Bethesda, Maryland; and USPHS Research Grant CA-06102-03.

² Deceased.

Received 3/ 4/65. Revised 8/16/65.