All three populations exist simultaneously in tumors. The cell cycle is composed of four phases during which the cell prepares for and effects mitosis. Cells that are committed to divide again enter the G 1 phase. Variations in these three factors are responsible for the variable rates of tumor growth observed among tumors of differing histologies, as well as among metastatic and primary tumors of the same histology. Tumors characteristically exhibit a sigmoid-shaped Gompertzian growth curve, in which tumor doubling time varies with tumor size.
Tumors grow most rapidly at small tumor volumes.
As tumors become larger, growth slows based on a complex process dependent on cell loss and tumor blood and oxygen supply. Using kinetic principles, a set of guidelines for designing modern combination chemotherapy regimens have been derived. Preferentially, drugs that induce complete remissions should be included. Drugs with different mechanisms of action should be combined in order to allow for additive or synergistic effects on the tumor. Drugs with differing dose-limiting toxicities should be combined to allow each drug to be given at full or nearly full therapeutic doses.