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 patients 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 cycles 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 relapse in patients who have achieved clinically complete remissions.
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