Rationale for chemotherapeutic approaches to prostate cancer.

The problems of curing tumors with a low growth fraction with cytotoxic chemotherapeutic agents include 1) the fact that such agents attack biochemical pathways common and vital to all cells, 2) the existence in a tumor of cells with both temporary and permanent resistance to specific agents, and 3) the exponential nature of cell kill, which necessitates a much more intensive treatment to effect cure than to effect remission. The possible bases for selectivity of anticancer drugs include those factors that affect the concentration of the active form of the drug at the active site, those that affect the drug receptor interaction and those that determine whether this interaction will lead to cell death. Possible ways of overcoming resistance include combination chemotherapy, more intensive chemotherapy, adjuvant chemotherapy, and maneuvers leading to recruitment of cells into cycle. Because of tumor cell heterogeneity a different approach may be needed to effect cure from that required to induce complete remission.