Mobilization, collection, and characterization of peripheral blood hemopoietic progenitors after chemotherapy with epirubicin, paclitaxel, and granulocyte‐colony stimulating factor administered to patients with metastatic breast carcinoma

We conducted a prospective randomized clinical trial to assess the mobilizing efficacy of filgrastim, lenograstim and molgramostim following a disease-specific chemotherapy regimen. Mobilization consisted of high-dose cyclophosphamide in 45 cases (44%), and cisplatin/ifosfamide/ etoposide or vinblastine in 22 (21%), followed by randomization to either filgrastim or lenograstim or molgramostim at 5 lg/kg/day. One hundred and three patients were randomized, and 82 (79%) performed apheresis. Forty-four (43%) patients were chemonaive, whereas 59 (57%) were pretreated. A median number of one apheresis per patient (range, 1-3) was performed. The median number of CD34 þ cells obtained after mobilization was 8.4 Â 10 6 /kg in the filgrastim arm versus 5.8 Â 10 6 /kg in the lenograstim arm versus 4.0 Â 10 6 /kg in the molgramostim arm (P ¼ 0.1). A statistically significant difference was observed for the median number of days of growth factor administration in favor of lenograstim (12 days) versus filgrastim (13 days) and molgramostim (14 days) (Po0.0001) and for the subgroup of chemonaive patients (12 days) versus pretreated patients (14 days) (Po0.001). In conclusion, all three growth factors were efficacious in mobilizing peripheral blood progenitor cells with no statistically significant difference between CD34 þ cell yield and the different regimens, and the time to apheresis is likely confounded by the different mobilization regimens.

Section: Pbpc Collectionmentioning

confidence: 99%

A randomized study comparing filgrastim versus lenograstim versus molgramostim plus chemotherapy for peripheral blood progenitor cell mobilization

Kopf

Giorgi

Vertogen

et al. 2006

“…1 Standard-dose epirubicin/paclitaxel combination plus cytokines are effective in mobilizing PBSCs with induction of white blood cell (WBC) nadirs of brief duration without severe thrombocytopenia. [2][3][4] Moreover, either high-dose epirubicin or high-dose paclitaxel followed by filgrastim are able to mobilize PBSCs in patients with breast cancer. 5,6 Cardiotoxicity was clearly documented by both clinical and laboratory cardiac evaluation, when high single doses of epirubicin were administered.…”

Section: Discussionmentioning

confidence: 99%

“…The median numbers of CD34+ cells collected per leukapheresis were 2.8 Â 10 6 /kg (range 1.2-7.8), 4.7 Â 10 6 / kg (range 0.72-11.7), and 6.3 Â 10 6 /kg (range 0.52-20.4), respectively. [2][3][4] However, it is difficult to compare data from PBSC mobilization performed in these three studies, because of the lack of standardization of CD34+ cell quantification assays, the different doses of paclitaxel used in combination with epirubicin 90 mg/m 2 in these three studies (135, 175, and 200 mg/m 2 , respectively), the variable number of courses of chemotherapy before harvesting, and the different characteristics of the patients.…”

Section: Discussionmentioning

confidence: 99%

High-dose epirubicin, preceded by dexrazoxane, given in combination with paclitaxel plus filgrastim provides an effective mobilizing regimen to support three courses of high-dose dense chemotherapy in patients with high-risk stage II–IIIA breast cancer

Giorgi

Rosti

Zaniboni

et al. 2003

Summary:We verified the possibility of collecting large amounts of peripheral blood stem cells (PBSCs) to support three courses of adjuvant high-dose dense chemotherapy (HDDC) with high-dose epirubicin, preceded by dexrazoxane, and high-dose paclitaxel, in patients with highrisk breast cancer (X9 positive nodes). The mobilizing regimen consisted of high-dose epirubicin 150 mg/m 2 , preceded by dexrazoxane 1000 mg/m 2 (day 1), given in combination with paclitaxel 175 mg/m 2 (day 2), plus filgrastim. Of the 25 patients enrolled, one went off study due to a severe hypersensitivity reaction to paclitaxel, another did not undergo leukapheresis due to fever persistent after hematological recovery, while in 23 patients an adequate number of PBSCs was collected by a single leukapheresis. The median number of CD34+, CD34+/CD33À, and CD34+/CD38À cells collected per patient was 17 Â 10 6 /kg, 13.4 Â 10 6 /kg, and 1.5 Â 10 6 / kg, respectively. Neutropenia was the only grade 4 toxicity and lasted a median of 3 days. High-dose epirubicin, preceded by dexrazoxane for the first time used in mobilizing regimen, and paclitaxel plus filgrastim are effective in releasing large amounts of PBSCs, which can then be safely employed to support multiple courses of HDDC. Bone Marrow Transplantation (2003) 32, 251-255. doi:10.1038/sj.bmt.1704125 Keywords: stem cell mobilization; breast cancer; dexrazoxane; epirubicin; paclitaxel; filgrastim The ideal mobilizing regimen for patients with cancer should be one that contains the most effective antitumor drugs, and that is able to produce a collection of an adequate amount of peripheral blood stem cells (PBSCs). Combination chemotherapy with epirubicin and paclitaxel is one of the most active regimens for patients with breast cancer. 1 Standard-dose epirubicin/paclitaxel combination plus cytokines are effective in mobilizing PBSCs with induction of white blood cell (WBC) nadirs of brief duration without severe thrombocytopenia. 2-4 Moreover, either high-dose epirubicin or high-dose paclitaxel followed by filgrastim are able to mobilize PBSCs in patients with breast cancer. 5,6 Cardiotoxicity was clearly documented by both clinical and laboratory cardiac evaluation, when high single doses of epirubicin were administered. 7 Dexrazoxane is a derivative of EDTA that has been shown to decrease significantly the incidence of cardiomyopathy in patients treated with anthracyclines. 8 Results of a randomized trial demonstrated that dexrazoxane protects against the development of cardiotoxicity when high single doses of epirubicin are used, without affecting antitumor activity. 7 No data are available regarding the use of dexrazoxane in combination with high-dose anthracyclines, with or without other agents, for PBSC mobilization.There is preclinical and clinical evidence that doseintensive chemotherapy has a greater antitumor effect in patients with breast cancer. 9-14 A number of different strategies for intensifying dose with PBSC support have been described. [15][16][17][18][19][20][21] The Norton-S...

“…19 These factors make it an optimal tool to mobilize PBPCs in breast cancer patients. Paclitaxel has been used alone 20 or combined with either CP 9,10,21-23 or epirubicin 24,25 for PBPC mobilization. CP has been tested with different schedules and doses, ranging for paclitaxel between 150-300 mg/m 2 and 2-4 g/m 2 for CP.…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells

Rey

Dansey

et al. 1999

Summary:Peripheral blood progenitor cells are now commonly used for hematologic reconstitution after myelosuppressive chemotherapy for hematologic and solid malignancies. The purpose of this study was to evaluate the activity of paclitaxel 170 mg/m 2 and cyclophosphamide 2 g/m 2 (CP) with filgrastim (human G-CSF) for mobilization of PBPCs as the first or second maneuver after failure with filgrastim alone. Sixty-four patients with stage II-IV breast cancer received (CP) followed by filgrastim (10 g/kg/day). In 35 (55%) this was the first maneuver while it was for salvage in 29 (45%) patients. The median number of aphereses was two (range, 1-7). In 83% of the patients apheresis was initiated on days 10-11 following chemotherapy. The median numbers of CD34 + cells/kg, CD34 + cells/apheresis/kg and total nucleated cells/kg collected were 8.7 × 10 6 (2.11-73.5), 3.97 × 10 6 (0.3-36.75) and 164.15 × 10 8 (9-660), respectively. All the patients yielded at least 2 × 10 6 CD34 + cells/kg. CP mobilization salvaged the 29 patients who failed mobilization with filgrastim alone. When used as first-line mobilization the yield of CD34 + cells × 10 6 /kg was higher than in the salvage group (16.93 vs 3.94, P Ͻ 0.001). Patients receiving CP as salvage reached the target of 5 × 10 6 CD34 + cells/kg in only 45% (13/29) of cases vs 94.3% as first maneuver. CP followed by filgrastim is a safe and effective regimen for the mobilization of PBPCs in patients with breast cancer and shows significant activity in patients who failed to mobilize with filgrastim, suggesting a higher mobilization potential.