Mobilization of peripheral blood stem cells with docetaxel and cyclophosphamide (CY) in patients with metastatic breast cancer: a randomized trial of 3 vs 4 g/m2 of CY

Abstract

Summary:The purpose of this study was to develop a regimen of docetaxel, cyclophosphamide (CY) and filgrastim for mobilization of peripheral blood stem cells (PBSC) in patients with metastatic breast cancer (n = 66). A phase I trial of CY 2, 3 or 4 g/m 2 with docetaxel 100 mg/m 2 , in consecutive cohorts of four patients each, did not reveal any dose-limiting toxicities and subsequent patients were randomized to receive 3 or 4 g/m 2 of CY. The median yield of CD34 ؉ cells from all patients was 11.06 ؋ 10 6 /kg (range, 0.03-84.77) from a median of two aphereses (range, 1-7); 6.52 ؋ 10 6 CD34 ؉ cells/kg/apheresis (range, 0.01-52.07). Target CD34 ؉ cell doses у у у2.5 and у у у5.0 ؋ 10 6 /kg were achieved in 89% and 79%, respectively. There were no statistically significant differences in CD34 ؉ cell yields or target CD34 ؉ cell doses achieved following 3 or 4 g/m 2 of CY. Patients with only one prior chemotherapy regimen yielded a median of 12.82 ؋ 10 6 CD34 ؉ cells/kg/ apheresis compared to 5.85 for those receiving у у у2 regimens (P = 0.03). It was concluded that the combination of docetaxel, 100 mg/m 2 , CY 3 g/m 2 without mesna could be administered with acceptable toxicity with collection of adequate quantities of PBSC from the majority of patients. Keywords: mobilization; docetaxel; cyclophosphamideThe role of HDC with PBSC support for the treatment of patients with breast cancer is controversial 1 despite the fact that numerous phase 2 studies 2-5 and one prospective randomized trial 6 have demonstrated superiority compared to conventional-dose therapies. Patients in complete remission (CR) appear to benefit more from HDC than patients not in CR. 4 Thus, one approach to improving outcomes for patients with metastatic breast cancer is to improve the CR rate prior to HDC with PBSC support.Theoretically, chemotherapy administered for mobilization of PBSC can be integrated into the treatment plan of patients scheduled to receive HDC. Previous studies in patients with metastatic breast cancer have evaluated induction followed by drug combinations including: cyclophosphamide (CY), etoposide, 7 CY, etoposide and cisplatin 5 and CY and paclitaxel for mobilization of PBSC. 8 The taxanes, paclitaxel and docetaxel, are active in the treatment of patients who have failed doxorubicin-based regimens and are increasingly being evaluated in initial treatment regimens. 9-17 The administration of paclitaxel or docetaxel prior to HDC with PBSC support is also being evaluated in patients with breast cancer. 18,19 In order to incorporate new chemotherapeutic agents into a treatment strategy of induction, mobilization of PBSC and HDC with PBSC support it is important to determine the efficacy of such agents for the mobilization of PBSC. The combination of paclitaxel 200 mg/m 2 , CY 3 g/m 2 and filgrastim can be administered with acceptable toxicity allowing collection of adequate quantities of PBSC from the majority of patients with breast cancer. 8,[20][21][22] The purpose of the current study was to determine if regimens of do...

Mobilization of Peripheral Blood Stem Cells in High-Risk Breast Cancer Patients Using G-CSF After Standard Dose Docetaxel

“…Our results demonstrate superiority of doxetaxel combined with GCSF when compared with G-CSF alone. This regimen also compares favorably with recently reported results using high doses of cyclophosphamide in addition to docetaxel and G-CSF (17). Previous studies have documented that another taxane, paclitaxel, is effective in mobilizing PBSCs in conjunction with G-CSF, and improves PBSC mobilization when added to high-dose cyclophosphamide (18).…”

Topotecan–filgrastim combination is an effective regimen for mobilizing peripheral blood stem cells

“…Febrile neutropenia occurred in only four patients (36%). This finding compares favorably with those of studies of high-dose cyclophosphamide 38 and of other chemotherapy-filgrastim mobilization regimens; [39][40][41] in those reports rates of febrile neutropenia ranged from 20% to 100%.…”

Docetaxel effectively mobilizes peripheral blood CD34+ cells

“…Other investigators have examined the ability of docetaxel to mobilize CD34 ϩ cells when used in combination with either cyclophosphamide 22 or an anthracycline. 23 Taken together, docetaxel-based regimens appear to very effective to mobilise CD34 ϩ cells.…”