A Screening System for Anti-Cancer Agents Based on the Therapeutic Index

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Abstract
The therapeutic index (LD5/CD95) has proved useful in expressing the therapeutic value of drugs and canalso be employed in a screening system. We have developed a screening system for substances effective in the treatment of cancer, using a well-known and proven substance as a standard. It has to be decided whether therapeutic index of the test substance is greater or less than that of the standard. A rough estimate of the LD5 is obtained, and a dose obtained by dividing this by the therapeutic index of the standard is administered to a random sample of n cancer subjects. The test substance is then selected provided the percentage of definite cures is greater than a response rate po, where Po and the number n are chosen so that a substance better than the standard is selected with at least some high probability, while a substance worse than the standard is selected with at most some small probability, n remaining as small as possible. An explicit expression for the response probability in this single stage process is obtained (formula (6)), subject to an approximate but plausible model. This formula agrees satisfactorily with empirical data. If the screening process involves several stages, it is advantageous to improve the estimate of LD5 at each stage.

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