High-dose chemotherapy supported by peripheral blood progenitor cells in poor prognosis metastatic breast cancer--phase I/II study

Abstract

Current treatments for metastatic breast cancer are not associated with significant survival benefits despite response rates of over 50%. High-dose therapy with autologous bone marrow transplantation (ABMT) has been investigated, particularly in North America, and prolonged survival in up to 25% of women has been reported, but with a significant treatment-related mortality. However, in patients with haematological malignancies undergoing autologous transplantation, haematopoietic reconstruction 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 PBPC mobilisation with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) after 12 weeks' infusional induction chemotherapy and the subsequent efficacy of the haematopoietic reconstitution after conditioning with melphalan and either etoposide or thiotepa. PBPC mobilisation was successful in 28/32 (88%) patients, and there was a rapid post-transplantation 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 the 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 chemotherapy is feasible after infusional induction chemotherapy for patients with metastatic breast cancer, although the optimum drug combination has not yet been determined.