Dose intensity as a therapeutic strategy in breast cancer

Summary

The results of systemic treatment for primary and metastatic breast cancer have plateaued in the past decade. The majority of oncologists continue to use the same chemotherapy regimens and endocrine therapies that were available in the mid 1970s. In metastatic breast cancer, still only 60–70% of patients can be expected to achieve a remission, with only 10–20% of these being a complete remission, which is usually of short duration. Metastatic breast cancer remains incurable today. Obviously, new treatment strategies are needed. The development of new active drugs, or the development of innovative ways of giving old drugs, has been disappointing in breast cancer. Similarly, combining hormones with chemotherapy, or the use of various biologic response modifiers, has not resulted in a major advance. One strategy that is currently undergoing active research is increased dose intensity of chemotherapy. This can be achieved by delivering extremely high doses of cytotoxic chemotherapy followed by hematopoietic support. A second approach involves delivering lower doses, but on a more frequent schedule than conventional programs. Preliminary results from phase II evaluation of these programs demonstrate high complete response rates, relatively short response durations, and considerable toxicity. However, 10–20% of patients treated with these regimens remain in complete remission several years after treatment, providing optimism that this approach may be effective in some patients. Advances in hematopoietic support, including autologous bone marrow transplantation (ABMT), peripheral stem cell administration, and the use of hematopoietic growth factors, have reduced toxicity. This strategy is now ready for phase III randomized trials in metastatic breast cancer as well as in the high-risk adjuvant patient to determine if high-dose therapy offers a worthwhile advantage in patients with breast cancer.