The Log-Kill Hypothesis

The log-kill hypothesis proposes that the magnitude of tumor cell kill by anticancer drugs is a logarithmic function. For example, a 3-log-kill dose of an effective drug reduces a cancer cell population of 1012 cells to 109 (a total kill of 999 × 109 cells); the same dose would reduce a starting population of 106 cells to 103 cells (a kill of 999 × 103 cells). In both cases, the dose reduces the numbers of cells by 3 orders of magnitude, or “3 logs.” A key principle that stems from this finding and that is applicable to hematologic malignancies is an inverse relationship between tumor cell number and curability Mathematical modeling data suggest that most human solid tumors do not grow in such an exponential manner and rather that the growth fraction of the tumor decreases with time owing to blood supply limitations and other factors. In drug-sensitive solid tumors, the response to chemotherapy depends on where the tumor is in its growth curve. Therefore, almost all antitumor agents have a steep dose-response curve for both toxic and therapeutic effects.