POTENTIAL STRATEGIES FOR IMPROVING THE RESULTS OF HIGH-DOSE CHEMOTHERAPY IN PATIENTS WITH METASTATIC BREAST-CANCER

High-dose chemotherapy (HDC) is the most effective approach for induci ng complete remissions in patients with metastatic breast cancer, and although most patients will relapse, a small percentage (10%-15%) achi eve durable remissions beyond five years. Additionally, HDC has produc ed five-year relapse-free survival rates in excess of 70% in patients with stage II breast cancer with >10 nodes. The use of HDC in breast c ancer remains controversial and randomised trials are required to asse ss the survival impact of this approach. The introduction of haematopo ietic growth factors (HGF) and peripheral blood progenitor cells (PBPC ) has advanced the use of HDC by reducing treatment-related mortality (from 20% to 5%) and by allowing the development of multiple cycles of intensive therapy. Based on tumour kinetic models we have hypothesise d that multiple, rapidly cycled courses of high-dose therapy may impro ve the rate of durable remission in metastatic breast cancer. The feas ibility of this approach has been shown in a series of pilot studies i n which one or more courses of high-dose cyclophosphamide and recombin ant granulocyte colony-stimulating factor (G-CSF) (filgrastim) were gi ven to obtain PBPC which were then used to support one or more courses of HDC. In successive studies the HDC component consisted of: a singl e course of carboplatin, etoposide and cyclophosphamide; four courses of carboplatin; tandem courses of thiotepa; or a sequence of melphalan and thiotepa. Promising response rates have been produced in advanced breast and ovarian cancer with the later generation of regimens. Thes e results justify the conduct of prospective randomised trials.