High dose chemotherapy in breast cancer reviewed

Laboratory and experimental data show a dose response curve for cytostatic drugs, especially for alkylating agents. For many malignancies, clinical evidence of a dose response relationship is limited. The dose limiting toxicity of most cytostatic drugs is myelosuppression, which can be circumvented by the use of haematopoietic growth factors and/or autologous bone marrow or peripheral stem cell support. Clinical data derived from studies in patients with metastatic breast cancer, show that dose escalations of 1.5-2 x standard dosages, possible without autologous bone marrow or peripheral stem cell transport can induce higher remission rates, which did not, however, correspond to a significant survival advantage. Despite promising results from small trials with high dose intensity treatment in combination with peripheral stem cell or bone marrow support (depending on the schedule used, dose escalations possible of 5-10 x the standard dosages) in a selected patient population with high risk or metastatic breast cancer, they do not justify the use of this approach outside the setting of clinical studies. We have to gain more knowledge of selecting the patients who are likely to profit from high dose chemotherapy as well as to continue focusing on improvement of efficacy, reduction of the considerable morbidity and costs of this treatment.