Dose Response for Adjuvant Chemotherapy of Breast Cancer: Experimental and Clinical Considerations

Preclinical experimental models of dose response in breast cancer will be presented. Dose response differs according to the agent. For example, for the alkylating agents drug resistance is generally difficult to produce experimentally, and a steep dose-response curve both in vitro and in vivo is maintained through multiple logs of cell kill (Frei et al. 1985, Frei et al., in press; Teicher et al. 1986). In contrast using nonalkylating agents, drug resistance of a high degree can be produced readily. Related to this is the fact that fractional cytoreduction is progressively compromised with increasing doses through a multilog cell kill model. In this regard, the alkylating agents more closely resemble radiotherapy. The lack of cross-resistance among the alkylating agents in both in vitro and in vivo models has important implications for clinical treatment strategies (Frei et al. 1985; Frei et al., in press; Teicher et al. 1986).