THE LOG CELL
Cytotoxic drugs act by first-order kinetics; that is, at a
given dose, they kill a constant fraction
of the tumor cells rather than a fixed number of cells. For example, a drug
dose that would result in a three-log cell kill (i.e., 99.9% cytotoxicity)
would reduce the tumor burden of an animal that has 108 leukemic
cells to 105 cells. This killing of a fraction of cells rather than
an absolute number per dose is called the log
cell kill hypothesis.
The earliest detectable human
cancers usually have a volume of at least 1 cc and contain 109 (1
billion) cells. This number reflects the result of at least 30 cycles of cell
division, or cell doublings, and represents a kineti-cally advanced stage in
the tumor’s growth. Most pa-tients actually have tumor burdens that are greater
than 109. Since the major limiting factor in chemotherapy is
cytotoxicity to normal tissues, only a limited log cell kill can be expected
with each individual treatment.
Even in the absence of tumor
regrowth, several cy-cles of therapy would be required for eradication of the
tumor, assuming it was sensitive to the drugs employed. When a tumor has
decreased in size to approximately 108 cells, it is generally no
longer detectable clinically and is considered a clinically complete remission.
Regrowth of residual cells is the obvious cause of re-lapse in patients who
have achieved clinically complete remissions.