ABSTRACT
Every tumor cell must be killed to cure a patient because even a single cancer cell is capable of eventually killing the host. The
fractional cell kill hypothesis
states that the efficacy of cytotoxic drugs obeys first order kinetics, i.e., a given drug concentration applied for a specific period of time will kill a constant fraction of the cell population, regardless of the absolute number of cells present. Each subsequent treatment cycle will kill the same fraction of the remaining cells. For example, if a tumor has 1 million cells and a particular treatment regimen has a 90% cell kill rate, the first treatment will leave 100,000 cells. Even if regrowth of the cancer cells doubles the number of cancer cells present by the time the next chemotherapy course is given, it is theoretically possible to eventually reduce the tumor cell population to only one cell which, hopefully, will be killed by the immune system (Figure 5.1a). In practice, the major bulk of the tumor is often removed by surgery prior to chemotherapy (Figure 5.1b). The fractional cell kill hypothesis does not consider the fact that cancer cells can mutate over time and, therefore, that an increasingly large proportion of the cells may become resistant to chemotherapy (Figure 5.1c). Also not considered is the fact that heterogeneous solid tumors grow slowly and are, therefore, less susceptible to cytotoxic agents.
