New approaches to adjuvant chemotherapy for breast cancer.

Adjuvant chemotherapy improves the disease-free and overall survival of patients with resectable, early-stage breast cancer. However, the effect is modest, and we need means of increasing its impact. Retrospective and prospective studies on the effects of increased drug dosage have demonstrated that within some dose ranges, increasing the dose intensity (total drug dose divided by total treatment time) improves the outcome of treatment. Dose escalation to higher levels, sufficient to require growth factor and autologous stem cell support, is the subject of ongoing randomized study. Because there are both theoretical and practical limits on the potential effectiveness of single-cycle, high-dose chemotherapy, researchers are developing alternative means of increasing the effect of chemotherapy. One theoretically advantageous approach, predicted to be superior by kinetic models, is "dose-dense" chemotherapy administration. This approach consists of multiple cycles of escalated-dose chemotherapy administered at very short intervals. When administering presumed non-cross-resistant regimens or agents with overlapping toxicity, clinicians can increase dose density by using the sequential treatment plan. Furthermore, this plan can also facilitate the addition of new active drugs.