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

Abstract

Summary 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 posttransplantation haematopoietic recovery: median time to neutrophils >0.5 x l091 -1 was 14 days and to platelets >20 x 109 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.

Mobilization of peripheral blood progenitor cells after induction chemotherapy (THP-doxorubicin-vinorelbine-cyclophosphamide-fluorouracil) and granulocyte colony-stimulating factor in breast cancer

“…Median levels of CD34 ϩ cells and CFU-GM harvested, respectively 7 ϫ 10 6 /kg and 124 ϫ 10 4 /kg, were similar to those obtained with different mobilization protocols (Table 4). [24][25][26][27][28]30 These prior results showed sufficient collection of PBPC for autologous transplantation.…”

“…However, since the limiting factor of TNCF treatment is the hematological toxicity, PBPC support would be required. Several protocols exist for PBPC recruitment, mainly cyclophosphamide (or ifosfamide) 24 and etoposide 19,25 and/or cisplatin 18 plus G-CSF, but induction chemotherapy can likewise be used in order to obtain both mobilizing and specific cytotoxic effects at the same time. To test this idea, Van der Wall 26 and D'Hont 27 mobilized PBPC with fluorouracil, epidoxorubicin and cyclophosphamide (FEC) chemotherapy associated with G-CSF in high-risk breast cancer.…”

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome

“…Keywords: CD34 + selection; PBSC transplantation; metastatic breast cancer High-dose chemotherapy (HDC) with peripheral blood stem cell (PBSC) transplantation has been shown to be effective in patients with metastatic carcinoma of the breast. [1][2][3][4] In patients who achieve a complete remission with chemotherapy, long-term disease-free survival can be obtained by a variety of different HDC regimens. 1,2,5,6 The use of high-dose chemotherapy with stem cell rescue has allowed dose-intensity to be maximized and morbidity and mortality to be reduced.…”

Tandem and triple high-dose chemotherapy with autologous stem cell rescue in metastatic breast cancer

“…Phase II studies in patients with MBC have shown high complete remission rates and a proportion of durable remissions in 15%± 20% (de Vries et al 1996, Cameron et al 1996Bitran et al 1996;Tokuda et al 1996;Somlo et al 1997;Broun et al 1995;Dunphy et al 1994;Ayash et al 1996; Antman et al 1992). In the ®rst prospective randomized trial of patients with MBC treated with either standard or tandem high-dose chemotherapy, showed that HDC resulted in an improvement in both progression-free survival (PFS) and overall survival (OAS).…”