HIGH-DOSE CHEMOTHERAPY SUPPORTED BY PERIPHERAL-BLOOD PROGENITOR CELLSIN POOR-PROGNOSIS METASTATIC BREAST-CANCER - A PHASE I II STUDY/

Current treatments for metastatic breast cancer are not associated wit h significant survival benefits despite response rates of over 50%. Hi gh-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survi val in up to 25% of women has been reported, but with a significant tr eatment-related. mortality. However, in patients with haematological m alignancies undergoing autologous transplantation, haematopoietic reco nstruction is significantly quicker and mortality lower than with ABMT , when peripheral blood progenitor cells (PBPCs) are used. In 32 women with metastatic breast cancer, we investigated the feasibility of PBP C mobilisation with high-dose cyclophosphamide and granulocyte colony- stimulating factor (G-CSF) after 12 weeks' infusional induction chemot herapy and the subsequent efficacy of the haematopoietic reconstitutio n after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there wa s a rapid posttransplantation haematopoietic recovery: median time to neutrophils > 0.5 x 10(9) l(-1) was 14 days and to platelets > 20 x 10 (9) l(-1) was 10 days. There was no procedure-related mortality, and t he major morbidity was mucositis (WHO grade 3-4) in 18/32 patients (56 %). In a patient group of which the majority had very poor prognostic features, the median survival from start of induction chemotherapy was 15 months. Thus, PBPC mobilisation and support of high-dose chemother apy is feasible after infusional induction chemotherapy for patients w ith metastatic breast cancer, although the optimum drug combination ha s not yet been determined.