Disease relevance of IMI 28

• METHODS: In an observational study in hospital and as outpatients, 92 patients with advanced breast cancer were treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000) [1].
• Epirubicin-induced primary Sjögren's syndrome [2].
• Production of the antitumor drug epirubicin (4'-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius [3].
• Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen [4].
• Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin [4].
• There is no specific barrier for epirubicin to reach primary breast cancer tumors [5].

Psychiatry related information on IMI 28

• Forty patients with advanced breast cancer, randomised to receive CMF or weekly low dose Epirubicin, were evaluated by UICC criteria of response and WHO toxicity criteria, in addition to three QoL instruments: the 'Qualitator' daily diary card, 4 weekly Nottingham Health Profile (NHP) and Linear Analogue Self-Assessment (LASA) [6].
• CONCLUSIONS: The combination of epirubicin, cisplatin and UFT showed anticancer activity against metastatic gastric adenocarcinoma, had a tolerable toxicity profile and showed excellent patient compliance [7].

High impact information on IMI 28

• Response of glassy-cell carcinoma of the cervix to cisplatin, epirubicin, and mitomycin C [8].
• The activation of caspase-8, a crucial upstream mediator of death receptor signaling, was investigated in epirubicin- and Taxol-induced apoptosis of B-lymphoma cells [9].
• PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients [10].
• In vivo therapy studies in a series of xenograft models featuring overexpression of EGFR and/or EGFRvIII showed the superiority of immunoliposomal delivery of encapsulated drugs, which included doxorubicin, epirubicin, and vinorelbine [11].
• Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide [12].

Chemical compound and disease context of IMI 28

• High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest [13].
• Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma [14].
• Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer [15].
• A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer [16].
• Increasing 4'-epidoxorubicin and fixed ifosfamide doses plus granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a pilot study [17].

Biological context of IMI 28

• Down-regulation of tau increased sensitivity of breast cancer cells to paclitaxel but not to epirubicin [18].
• However, the pharmacokinetics of epirubicin at high doses have never been reported [19].
• The maximum tolerated dose was 150 mg/m2 epirubicin given either as a bolus or as an infusion [19].
• Area under the concentration-time curve (AUC) of epirubicin was higher in the TE group (2,346 ng/mL. h v 1,717 ng/mL. h; P =.002) [20].
• Of 39 patients receiving epirubicin who had serial cardiac assessments, five sustained left ventricular ejection fraction falls of 10% or more and two patients developed congestive cardiac failure at cumulative doses of 178 mg/m2 and 833 mg/m2 [21].

Anatomical context of IMI 28

• Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone [22].
• Comparative study of dose escalation versus interval reduction to obtain dose-intensification of epirubicin and cyclophosphamide with granulocyte colony-stimulating factor in advanced breast cancer [23].
• During steady state there was a linear relationship between epirubicin dose administered and epirubicin level in plasma (r = .58, P less than .05), whole blood (r = .75, P less than .005), and in leukocytes (r = .68, P less than .05) [24].
• An inverse linear correlation between epirubicin AUC and neutrophil recovery was also observed (P =.012) [20].
• Distribution and toxic effects of intravenously injected epirubicin on the central nervous system of the mouse [25].

Associations of IMI 28 with other chemical compounds

• Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product [26].
• PATIENTS AND METHODS: Thirty-five patients were treated with three cycles of induction chemotherapy with epirubicin 50 mg/m(2) and cisplatin 75 mg/m(2) combined with continuous-infusion 5-FU 200 mg/m(2) daily for 9 weeks, followed by concurrent chemoradiation of 60 Gy in 2-Gy fractions with cisplatin 20 mg/m(2) daily for 5 days in weeks 1 and 6 [27].
• We studied the effect of cyclosporin A (CsA) and two nonimmunosuppressive analogues, 11-methyl-leucine- (11-Me-Leu-CsA) and 6-methyl-alanine-cyclosporin A (6-Me-Ala-CsA), on the action of doxorubicin (DOX) and 4'-epidoxorubicin against parent (AuXB1) and multidrug-resistant (CHRC5) Chinese hamster ovary cells [28].
• PURPOSE: To determine the maximum-tolerated dose (MTD) of 4'-epidoxorubicin (EPI) in combination with full dose of ifosfamide (IFO) when granulocyte-macrophage colony-stimulating factor (GM-CSF) was used, to estimate its clinical efficacy, and to evaluate the mobilization of hematopoietic progenitors [17].
• However, DAC treatment sensitizes the xenografts to cisplatin, carboplatin, temozolomide, and epirubicin [29].
• Epirubicin also formed approximately 60% less alcohol metabolites than doxorubicin, but this was caused primarily by its higher Km and lower Vmax values for two-electron carbonyl reduction by aldo/keto-reductases of human cardiac cytosol [30].

Gene context of IMI 28

• The 3' end of the MRP6 protein was found to be almost identical with the anthracycline resistance associated (ARA) protein identified previously in epirubicin-selected leukemia cells [31].
• For lung resistance-related protein, this association was limited to 5-fluorouracil, Adriamycin/epirubicin, and cyclophosphamide [32].
• UGT2B7 is the major human UGT catalyzing epirubicin glucuronidation, and UGT2B7 is the candidate gene for this phenotype [33].
• We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels, but not circulating VEGF levels, predict a poor outcome [34].
• Over-expression of ABCG2 in cell lines confers resistance on a wide variety of anticancer drugs including mitoxantrone, daunorubicin, doxorubicin, topotecan and epirubicin [35].

Analytical, diagnostic and therapeutic context of IMI 28

• Indeed, active caspase-8 was readily detected after treatment of mature and immature B-lymphoid cells with epirubicin or Taxol [9].
• Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group [36].
• CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone [37].
• Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer [38].
• CONCLUSION: Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival [39].

References