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

Abstract

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...

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

“…Grade 4 neutropenia occurred in 72 (70%) patients: 28 (74%) in the filgrastim arm, 19 (53%) the lenograstim arm and 25 (86%) in the molgramostim, respectively. Median duration to recovery of ANC40.5 Â 10 9 /l was 4 days (range, 1-18) in the filgrastim arm, 3 days (range, 1-15) in the lenograstim arm and 6 days (range, [3][4][5][6][7][8][9][10][11] in the molgramostim arm. The difference among the three treatment arms was statistically significant in favor of lenograstim for both parameters: frequency and duration of neutropenia (P ¼ 0.001 and 0.0005, respectively).…”

“…1 PBPC collection is performed after administration of diseasespecific mobilizing chemotherapy followed by a myeloid growth factor, as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). [2][3][4] A strong correlation between the number of PBPC collected and then reinfused and the hematological recovery after high-dose chemotherapy has been demonstrated. 5 As consequence, it is of paramount importance to identify the best myeloid growth factor to improve PBPC collection.…”

Multiple cycles of PBPC-supported high-dose carboplatin and paclitaxel following mobilization with epirubicin and cisplatin are feasible but ineffective in treating patients with advanced non-small cell lung cancer

“…The median number of CD34 þ cells collected per leukapheresis was 2.8 Â 10 6 /kg (range: 1.2-7.8), 4.7 Â 10 6 /kg (range: 0.7-11.7), 6.3 Â 10 6 /kg (range: 0.5-20.4) and 17 Â 10 6 /kg (range: 4.5-38.4), respectively. [5][6][7][8] However, it is difficult to compare data from PBPC mobilizations performed in these four studies, because of the lack of standardization of CD34 þ cell quantification assays, the different doses of drugs used in these studies, the variable number of courses of chemotherapy before harvesting and the different characteristics of the patients.…”

“…The median of 13.5 Â 10 6 CD34 þ cells/kg collected per patient was similar to that of our previous study with epirubicin (150 mg/m 2 ) followed by filgrastim. 8 This is a historical comparison in a different patient population with no statistical significance, but it is likely that no less PBPCs can be collected by adding cisplatin. Moreover, none of the patients developed clinically relevant toxicities, therefore the use of cisplatin in combination with high-dose epirubicin may be considered justified to give the most active chemotherapeutic drugs in the mobilizing phase.…”

“…[2][3][4] High-dose epirubicin either as single agent or in combination with taxanes followed by filgrastim is able to mobilize PBPCs with induction of WBC nadirs of brief duration without severe thrombocytopenia in patients with several neoplasms. [5][6][7][8][9] There is preclinical and clinical evidence that dose-intensive epirubicin-based chemotherapy has a greater antitumor effect in patients with NSCLC. [10][11][12] Standard-dose platinum-based and/or taxane-based two-drug combination are the most active regimens for patients with NSCLC.…”