High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

Cottu, P.; Jm, Extra; Espié, Marc; Marolleau, Jean Pierre; Makke, J; Micléa, J.-M.; Laurence, Valérie; Mayeur, Didier; Lerebours, Florence; Cuvier, C.; Marty, M.

doi:10.1054/bjoc.2001.2069

Cited by 5 publications

(2 citation statements)

References 28 publications

(39 reference statements)

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“…An effect was also observed for chemotherapy regimen such that post-chemotherapy sP-selectin levels were highest in women who had received epirubicin, cytoxan, 5fluorouracil treatment. We are not aware of any literature suggesting that epirubicin, cytoxan, 5fluorouracil treatment differentially activates platelets compared to adriamycin (Cottu et al, 2001;Ottosson et al, 1999).…”

Section: Discussionmentioning

confidence: 96%

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Mills

Ancoli‐Israel

Parker

et al. 2008

Brain, Behavior, and Immunity

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Although chemotherapy for breast cancer can increase inflammation, few studies have examined predictors of this phenomenon. This study examined potential contributions of demographics, disease characteristics, and treatment regimens to markers of inflammation in response to chemotherapy for breast cancer. Thirty-five women with stage I -III-A breast cancer (mean age 50 years) were studied prior to cycle 1 and prior to cycle 4 of anthracycline-based chemotherapy. Circulating levels of inflammatory markers with high relevance to breast cancer were examined, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), Interleukin-1 receptor antagonist (IL1-RA), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), Interleukin-(IL-6), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf). Chemotherapy was associated with elevations in VEGF (p≤0.01), sICAM-1 (p≤0.01), sP-selectin (p≤0.02) and vWf (p≤0.05). Multiple regression analysis controlling for age and body mass index (BMI) showed that higher post-chemotherapy levels of inflammation were consistently related to higher prechemotherapy levels of inflammation (p's ≤0.05) as well as to certain disease characteristics. Postchemotherapy IL-6 levels were higher in patients who had larger tumors (p≤0.05) while postchemotherapy VEGF levels were higher in patients who had smaller tumors (p≤0.05). Postchemotherapy sP-selectin levels were highest in women who had received epirubicin, cytoxan, 5fluorouracil chemotherapy (p≤0.01). These findings indicate that chemotherapy treatment can be associated with elevations in certain markers of inflammation, particularly markers of endothelial and platelet activation. Inflammation in response to chemotherapy is most significantly related to inflammation that existed prior to chemotherapy but also potentially to treatment regimen and to certain disease characteristics.

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Section: Discussionmentioning

confidence: 96%

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Mills

Ancoli‐Israel

Parker

et al. 2008

Brain, Behavior, and Immunity

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“…[9][10][11][12][13][14] A number of different strategies for intensifying dose with PBSC support have been described. [15][16][17][18][19][20][21] The Norton-Simon model predicts that multiple, rapidly recycled applications of chemotherapy (dose dense) are more likely to eradicate residual cancer cells than either single or multiple applications with long intervals between cycles. 22 High-dose dense is an evolution of the dose-dense concept with an enhanced dose of the delivered drugs.…”

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

Bone Marrow Transplant

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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...

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Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients

Hénin

Meille

Barbolosi

et al. 2016

Breast Cancer Res Treat

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The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2-negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined.

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High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

Cited by 5 publications

References 28 publications

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer

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

Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients

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