Dose and schedule as determinants of outcomes in chemotherapy for breast cancer

Abstract

Many cytotoxic agents for the adjuvant treatment of breast cancer are available, but they have produced only modest results, even when the tumor burden is low. This relative lack of efficacy may be attributed, in part, to the nonspecificity of the current regimens. Additionally, there is evidence that the chemotherapy doses used in clinical practice are not optimal, which potentially compromises the outcomes when the thresholds of dose intensity are not reached. Variations in treatment underscore the need to return to the basics of chemotherapy administration: dose, schedule, concentration threshold, and therapeutic index. In patients with metastatic breast cancer a clear dose-response curve has been shown with some agents, including anthracyclines. The E-max model, which in its simplest form assumes a direct relation between the dose of a drug and its effect, may be used to improve dosing in the adjuvant treatment of breast cancer. Consistent with this model, threshold effects have been observed in treatment with both anthracyclines and paclitaxel for breast cancer. There is also evidence that using dose-dense schedules may produce better outcomes with some regimens. Maintaining chemotherapy agents at full dose on schedule is crucial to treatment success, especially in adjuvant therapy. Consequently, treatment practices should use both dose intensity and dose compression to increase the likelihood of positive outcomes in patients with breast cancer.