| Abstract: | The development of more effective treatment strategies currently provides the only realistic hope of reducing breast cancer mortality. Among such treatments, the use of high-dose chemotherapy (HDC) has been proposed as a potentially curative strategy. Consideration of the factors involved in the successful treatment of human tumours suggests that HDC is rationally planned with regard to tumour kinetics as well as chemotherapy sensitivity and resistance patterns. Ideally HDC should include dose escalation of at least 5–10-fold of drugs shown to have a steep dose-response curve and that have been effective in first-line treatment of breast cancer. Many current chemotherapy regimens lack one or the other of these attributes. Two randomized studies of HDC in breast cancer have been recently published. In the first study, HDC using a combination of cyclophosphamide, mitoxantrone and VP-16 as initial treatment was compared with a conventional-dose regimen consisting of cyclophosphamide, mitoxantrone and vincristine. The second study compared the effects of early or delayed HDC in patients who had achieved an optimal response to conventional-dose ‘induction’chemotherapy. Both studies showed HDC to be more effective than conventional-dose treatment in delaying time to progression but only the study that used HDC as initial treatment showed an effect of HDC on survival. The differences between these two investigations can probably be explained on the basis of the different effects on tumour kinetics and the efficiency of HDC when used as salvage therapy in the delayed HDC group. The finding that 20–25% of patients receiving HDC for metastatic breast cancer show prolonged disease-free survival suggest that HDC has an established role in the treatment of breast cancer. Attention now needs to turn to methods of optimizing this treatment strategy. |
