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Epirubicin HCl

Alias: 4'-epidoxorubicin HCl; 4'-Epidoxorubicin hydrochloride; IMI28; 4-epi DX; EPI; epi DX; 4-epiadriamycin; 4-epidoxorubicin; 4-epidoxorubicin HCl; epiADR; epidoxorubicin; epidorubicin; IMI 28; IMI-28; brand name: Ellence; Pharmorubicin PFS; Pharmorubicin; Farmorubicin; Farmorubicina; Epirubitec;
Cat No.:V1395 Purity: ≥98%
Epirubicin HCl (formerly 4'-epidoxorubicin; epiADR; epidoxorubicin; IMI 28; IMI-28; Ellence; Pharmorubicin PFS), the hydrochloride salt of the 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin, is a new anthracycline analog and a semisynthetic L-arabino derivative of doxorubicin approved as an anticancer medication.
Epirubicin HCl
Epirubicin HCl Chemical Structure CAS No.: 56390-09-1
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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Other Forms of Epirubicin HCl:

  • Epirubicin (4'-Epidoxorubicin)
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Top Publications Citing lnvivochem Products
InvivoChem's Epirubicin HCl has been cited by 1 publication
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Epirubicin HCl (formerly 4'-epidoxorubicin; epiADR; epidoxorubicin; IMI 28; IMI-28; Ellence; Pharmorubicin PFS), the hydrochloride salt of the 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin, is a new anthracycline analog and a semisynthetic L-arabino derivative of doxorubicin approved as an anticancer medication. Doxorubicin is a powerful anticancer drug, but its cumulative dose-dependent cardiotoxicity limits its application. Compared to doxorubicin, epirubicin HCl has a better therapeutic index and, at equivalent doses, is less toxic to the heart and blood vessels. Antineoplastic agent epirubicin HCl works by preventing Topoisomerase from doing its job. By intercalating into DNA and interacting with topoisomerase II, epirubicin prevents RNA and protein synthesis as well as DNA replication and repair. In addition, this agent interacts with the lipids in cell membranes to produce toxic free-radical intermediates and lipid peroxidation.

Biological Activity I Assay Protocols (From Reference)
Targets
Topoisomerase
ln Vitro

Epirubicin hydrochloride (4'-Epidoxorubicin hydrochloride), like doxorubicin, interferes with the synthesis of DNA, RNA, and proteins and damages DNA as a means of achieving its antitumor effects. The integrity and functionality of cellular membranes may also be impacted by epirubicin hydrochloride. Epirubicin hydrochloride maximally kills cells during the S phase of the cell cycle. Effects are also observed in the early G2, G1, and M phases at higher concentrations[1].
Epirubicin hydrochloride exhibit antitumor activity against the majority of cancerous cells. With an IC50 of 1.6 μg/mL after 24 hours, epirubicin hydrochloride is cytotoxic to Hepatoma G2 cells. 1.6 μg/mL Hep G2 cells undergo apoptosis when exposed to epirubicin hydrochloride, which also increases catalase activity by 50%, serine-dependent glutathione peroxidase activity by 110%, and the activity of Cu, Zn-superoxide dismutase by 172% and Mn-superoxide dismutase by 135%. NADPH-CYP 450 reductase is expressed more in cells when epirubicin hydrochloride is present, whereas GST-π expression is decreased[3].

ln Vivo
Epirubicin hydrochloride (4'-Epidoxorubicin hydrochloride) exhibits clinical efficacy against a diverse array of tumor types, such as gastrointestinal cancer, head and neck cancer, ovarian cancer, prostatic carcinoma, transitional bladder carcinoma, breast cancer, malignant lymphomas, soft tissue sarcomas, lung cancer, pleural mesothelioma, and so forth[4].
Epirubicin hydrochloride reduces the tumor mass of the human breast tumor xenograft R-27 by 74.4% when given at a dose of 3.5 mg/kg[5].
Enzyme Assay
Reporter assays[2]
For the NF-κB-dependent reporter assay, HEK293/NF-κB-RE/Foxp3 cells (1.5×104) or HEK293/NF-κB-RE cells (1.5×104) were seeded into white 96-well plates (Corning) and incubated overnight at 37°C in 5% CO2. These cells were treated with test drugs for 1 h. The cells were then stimulated with 0.3 ng/mL recombinant human TNF-α for 2.5 h. The medium was aspirated off and Steady-Glo (Promega) was added to the cells. The plate was then placed on a shaker for 10 min. Luminescence was detected using an ARVO Light plate reader.[2]
Forkhead box protein p3 (Foxp3) is crucial to the development and suppressor function of regulatory T cells (Tregs) that have a significant role in tumor-associated immune suppression. Development of small molecule inhibitors of Foxp3 function is therefore considered a promising strategy to enhance anti-tumor immunity. In this study, we developed a novel cell-based assay system in which the NF-κB luciferase reporter signal is suppressed by the co-expressed Foxp3 protein. Using this system, researchers screened a chemical library consisting of approximately 2,100 compounds and discovered that a cancer chemotherapeutic drug epirubicin restored the Foxp3-inhibited NF-κB activity in a concentration-dependent manner without influencing cell viability. Using immunoprecipitation assay in a Treg-like cell line Karpas-299, we found that epirubicin inhibited the interaction between Foxp3 and p65. In addition, epirubicin inhibited the suppressor function of murine Tregs and thereby improved effector T cell stimulation in vitro. [2]
Cell Assay
A 96-well plate is plated with 500 monolayer Hep G2 cells per well. The following day, epirubicin is added to the medium and the cells are treated. 15% volume of MTT dye solution is added at the conclusion of the incubation times. An equal volume of solubilization/stop solution (dimethylsulfoxide) is added to each well for an additional hour of incubation at 37°C after the first hour of incubation. At 570 nm, the reaction solution's absorbance is measured.
Epirubicin HCl is a new anthracycline analog and derivative of doxorubicin. Doxorubicin is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin HCl has more favorable therapeutic index than doxorubicin and possesses less hematologic and cardiac toxicity at comparable doses. Hepatoma G2 cells are a valuable model to study hepatocellular carcinoma and the liver, where drugs are metabolized. The goal of our study was to evaluate the cytotoxic effect of epirubicin HCl on viability of Hep G2 cells measured using the MTT cytotoxicity test. Epirubicin HCl produced a concentration- and time-dependent cytotoxicity to Hep G2 cells. The mechanism of cytotoxicity of epirubicin HCl (IC(50) value of 1.6 mug/ml within 24 h) appeared to involve a production of free radical species since activities of free radical scavenging enzymes (SOD, catalase, Se-dependent GPx) were increased. Addition of SOD prevented cytotoxicity of epirubicin HCl, and also counteracted the apoptosis. DNA fragmentation was determined to evaluate apoptosis. Western blot analysis indicated a decrease in GST-pi expression and increased activity of NADPH-dependent cytochrome P450 reductase which is a major enzyme in the conversion of epirubicin HCl to a free radical. It is proposed that production of reactive oxygen species increased by the treatment with epirubicin HCl can cause lipid peroxidation, which subsequently promotes apoptosis and reduces cell viability. Superoxide dismutase, catalase and glutathione peroxidase must be considered as a part of the intracellular antioxidant defense mechanism of Hep G2 cells against single electron reducing quinone-containing anticancer antibiotics.[3]
Animal Protocol
Mouse in vivo assays At day 0, female BALB/c mice (8 mice per group) were inoculated subcutaneously with CMS5a cells into the right inguinal region. Epirubicin (0.1, 0.3 or 1 mg/kg) or saline was given at days 3, 5 and 7 intravenously. On day 8, mice were euthanized and tumors were removed. Tumor-infiltrating lymphocytes (TIL) were dissociated from tumors using a gentleMACS dissociator according to the manufacturer’s instructions. The collected cells were seeded in 24-well plates and stimulated with phorbol 12-myristate 13-acetate (PMA) and Ionomycin at 37°C for 1 h, and then cultured for 6 h with GolgiPlug™. The cells were harvested and stained with PreCP-Cy™5.5 rat anti-mouse CD4 antibody and V500 rat anti-mouse CD8a antibody at 4°C for 15 min. The stained cells were fixed with Fixation/Permeabilization Concentrate and Diluent (1:3) at 4°C overnight. After washing, Permeabilization Buffer was added and the fixed cells were stained with PE-conjugated anti-mouse/rat Foxp3, anti-mouse IFN-γ-APC, and PE-conjugated anti-mouse IL-2 antibodies. The stained cells were analyzed using a FACS Canto II flow cytometer [2].
Dissolved in saline; 3.5 mg/kg; i.v. injection
Human breast tumor xenograft R-27
ADME/Pharmacokinetics
Absorption 100%

Route of Elimination Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary excretion.

Volume of Distribution
21 ± 2 L/kg [60 mg/m2 Dose]
27 ± 11 L/kg [75 mg/m2 Dose]
23 ± 7 L/kg [120 mg/m2 Dose]
21 ± 7 L/kg [150 mg/m2 Dose]

Clearance
65 +/- 8 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 60 mg/m2]
83 +/- 14 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 75 mg/m2]
65 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 120 mg/m2]
69 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 150 mg/m2]

Metabolism / Metabolites
Extensively and rapidly metabolized in the liver. Epirubicin is also metabolized by other organs and cells, including red blood cells. The four main metabolic routes are: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol exhibits in vitro cytoxic activity (~10% that of epirubicin), but it is unlikely to reach sufficient concentrations in vivo to produce cytotoxic effects.

Epirubicin is extensively and rapidly metabolized by the liver and is also metabolized by other organs and cells, including red blood cells. Four main metabolic routes have been identified: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol has in vitro cytotoxic activity one-tenth that of epirubicin. As plasma levels of epirubicinol are lower than those of the unchanged drug, they are unlikely to reach in vivo concentrations sufficient for cytotoxicity. No significant activity or toxicity has been reported for the other metabolites. NIH; DailyMed. Current Medication Information for Ellence (Epirubicin Hydrochloride) Injection, Solution (Updated: November 2014). Available from, as of June 16, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0a03c798-a652-4895-b29c-3b521a89ba42

Secondary alcohol metabolites have been proposed to mediate chronic cardiotoxicity induced by doxorubicin (DOX) and other anticancer anthracyclines. In this study, NADPH-supplemented human cardiac cytosol was found to reduce the carbonyl group in the side chain of the tetracyclic ring of doxorubicin, producing the secondary alcohol metabolite doxorubicinol (DOXol). A decrease in the level of alcohol metabolite formation was observed by replacing doxorubicin with epirubicin (EPI), a less cardiotoxic analogue characterized by an axial-to-equatorial epimerization of the hydroxyl group at C-4 in the amino sugar bound to the tetracyclic ring (daunosamine). A similar decrease was observed by replacing doxorubicin with MEN, a novel anthracycline with preclinical evidence of reduced cardiotoxicity. MEN is characterized by the lack of a methoxy group at C-4 in the tetracyclic ring and by intercalation of 2, 6-dideoxy-L-fucose between daunosamine and the aglycone. Multiple comparisons with methoxy- or 4-demethoxyaglycones, and a number of mono- or disaccharide 4-demethoxyanthracyclines, showed that both the lack of the methoxy group and the presence of a disaccharide moiety limited alcohol metabolite formation by MEN. Studies with enzymatically generated or purified anthracycline secondary alcohols also showed that the presence of a disaccharide moiety, but not the lack of a methoxy group, made the metabolite of MEN less reactive with the [4Fe-4S] cluster of cytoplasmic aconitase, as evidenced by its limited reoxidation to the parent carbonyl anthracycline and by a reduced level of delocalization of Fe(II) from the cluster. Collectively, these studies (i) characterize the different influence of methoxy and sugar substituents on the formation and [4Fe-4S] reactivity of anthracycline secondary alcohols, (ii) lend support to the role of alcohol metabolites in anthracycline-induced cardiotoxicity, as they demonstrate that the less cardiotoxic EPI and MEN 10755 share a reduction in the level of formation of such metabolites, and (iii) suggest that the cardiotoxicity of MEN might be further decreased by the reduced [4Fe-4S] reactivity of its alcohol metabolite. Minotti G et al; Chemm Res Toxicol 13 (12): 1336-41 (2000)

Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. ... Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. ... No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. ... /The authors/ findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces. PMID:11057412 Pilger A et al; Int Arch Occup Environ Health 73 (7): 442-8 (2000)

There is compelling in-vitro evidence that the evaluation of doxorubicin or epirubicin pharmacokinetics based solely on plasma concentration may not fully elucidate the differences between the two drugs. Both compounds bind to erythrocytes and their different binding to hemoglobin may influence their disposition in the body. The purpose of the present study was to compare the pharmacokinetics and metabolism of doxorubicin and epirubicin based on the plasma concentration, amount associated with blood cells and simultaneous monitoring of biliary and urinary elimination of unchanged drug and metabolites after single- and multiple-dose injections. The level of sarcoplasmic reticulum Ca2+ATPase in the heart was also measured as a biomarker of cardiotoxicity. Male Sprague-Dawley rats were treated in a parallel design with doxorubicin or epirubicin on a multiple-dosing basis (4 mg kg(-1) per week) or as a single dose injection (20 mg kg(-1)). Blood, urine and bile samples were collected periodically after each dose in the multiple-dosing regimen and the single dose injection, and at the end of each experiment the hearts were removed. The concentrations of each drug in plasma, blood cells, bile and urine samples were determined, and by simultaneous curve-fitting of plasma and bile data according to compartmental analysis, the pharmacokinetic parameters and constants were estimated. The concentration of drug associated with blood cells was analyzed according to non-compartmental analysis. The bile and urine samples provided the in-vivo metabolic data. The level of Ca2+ATPase in the heart, determined by Western blotting, was used as the toxicodynamic parameterto correlate with the kinetic data. Multiple-dosing regimens reduced the total plasma clearance and increased the area under the plasma concentration-time curve of both drugs. Also, the area under the curve of doxorubicin associated with blood cells increased with the weekly doses, and the related mean residence time (MRT) and apparent volume of distribution (Vdss) were steadily reduced. In contrast to doxorubicin, the mean residence time and Vdss of epirubicin increased significantly. Metabolic data indicated significant differences in the level of alcohol and aglycones metabolites. Doxorubicinol and doxorubicin aglycones were significantly greater than epirubicinol and epirubicin aglycone, whereas epirubicinol aglycone was greater than doxorubicinol aglycone. The area under the blood cells concentration-time curve correlated linearly with the changes in Ca2+ATPase net intensity. The results of this study demonstrate the importance of the kinetics of epirubicin and doxorubicin associated with blood cells. Linear correlation between the reduction of net intensity of the biomarker with the area under the curve of doxorubicin associated with blood cells confirms that the differences between the two compounds are related to their interaction with blood cells. This observation together with the observed differences in metabolism may underline a significant role for blood cells in distribution and metabolism of doxorubicin and epirubicin. Ramanathan-Girish S, Boroujerdi M; J Pharmacol 53 (7): 987-97 (2001)

Extensively and rapidly metabolized in the liver. Epirubicin is also metabolized by other organs and cells, including red blood cells. The four main metabolic routes are: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol exhibits in vitro cytoxic activity (~10% that of epirubicin), but it is unlikely to reach sufficient concentrations in vivo to produce cytotoxic effects. Route of Elimination: Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary excretion. Half Life: Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively

Biological Half-Life Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively

... Epirubicin pharmacokinetics may be described by a 3-compartment model, with median half-life values of 3.2 minutes, 1.2 and 32 hours for each phase. ... PMID:8070217
Toxicity/Toxicokinetics
Toxicity Summary
IDENTIFICATION AND USE: Epirubicin is red-orange crystals that are formulated into a solution for intravenous administration. It is used as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer. HUMAN EXPOSURE AND TOXICITY: Instances of administration of doses higher than recommended have been reported at doses ranging from 150 to 250 mg/sq m. The observed adverse events in these patients were qualitatively similar to known toxicities of epirubicin. Most of the patients recovered with appropriate supportive care. Secondary acute myelogenous leukemia (AML) has been reported in patients with breast cancer treated with anthracyclines, including epirubicin. Cardiac toxicity, including fatal congestive heart failure (CHF), may occur either during therapy with epirubicin or months to years after termination of therapy. Epirubicin was clastogenic in vitro (chromosome aberrations in human lymphocytes) both in the presence and absence of metabolic activation. ANIMAL STUDIES: Conventional long-term animal studies to evaluate the carcinogenic potential of epirubicin have not been conducted, but intravenous administration of a single 3.6 mg/kg epirubicin dose to female rats approximately doubled the incidence of mammary tumors (primarily fibroadenomas) observed at 1 year. Administration of 0.5 mg/kg epirubicin intravenously to rats every 3 weeks for ten doses increased the incidence of subcutaneous fibromas in males over an 18-month observation period. In addition, subcutaneous administration of 0.75 or 1.0 mg/kg/day to newborn rats for 4 days on both the first and tenth day after birth for a total of eight doses increased the incidence of animals with tumors compared to controls during a 24-month observation period. Administration of 0.8 mg/kg/day intravenously of epirubicin to rats during days 5 to 15 of gestation was embryotoxic (increased resorptions and post-implantation loss) and caused fetal growth retardation (decreased body weight), but was not teratogenic up to this dose. Administration of 2 mg/kg/day intravenously of epirubicin to rats on days 9 and 10 of gestation was embryotoxic (increased late resorptions, post-implantation losses, and dead fetuses; and decreased live fetuses), retarded fetal growth (decreased body weight), and caused decreased placental weight. This dose was also teratogenic, causing numerous external (anal atresia, misshapen tail, abnormal genital tubercle), visceral (primarily gastrointestinal, urinary, and cardiovascular systems), and skeletal (deformed long bones and girdles, rib abnormalities, irregular spinal ossification) malformations. Administration of intravenous epirubicin to rabbits at doses up to 0.2 mg/kg/day during days 6 to 18 of gestation was not embryotoxic or teratogenic, but a maternally toxic dose of 0.32 mg/kg/day increased abortions and delayed ossification. Administration of a maternally toxic intravenous dose of 1 mg/kg/day epirubicin to rabbits on days 10 to 12 of gestation induced abortion, but no other signs of embryofetal toxicity or teratogenicity were observed. When doses up to 0.5 mg/kg/day epirubicin were administered to rat dams from day 17 of gestation to day 21 after delivery, no permanent changes were observed in the development, functional activity, behavior, or reproductive performance of the offspring. In fertility studies in rats, males were given epirubicin daily for 9 weeks and mated with females that were given epirubicin daily for 2 weeks prior to mating and through day 7 of gestation. When dose of 0.3 mg/kg/day was administered to both sexes, no pregnancies resulted. No effects on mating behavior or fertility were observed at 0.1 mg/kg/day, but male rats had atrophy of the testes and epididymis, and reduced spermatogenesis. The 0.1 mg/kg/day dose also caused embryolethality. An increased incidence of fetal growth retardation was observed in these studies at 0.03 mg/kg/day. Multiple daily doses of epirubicin to rabbits and dogs also caused atrophy of male reproductive organs. Single 20.5 and 12 mg/kg doses of intravenous epirubicin caused testicular atrophy in mice and rats, respectively. A single dose of 16.7 mg/kg epirubicin caused uterine atrophy in rats. Epirubicin was mutagenic in vitro to bacteria (Ames test) either in the presence or absence of metabolic activation and to mammalian cells (HGPRT assay in V79 Chinese hamster lung fibroblasts) in the absence but not in the presence of metabolic activation. Epirubicin was clastogenic in vivo (chromosome aberration in mouse bone marrow). Hazardous Substances Data Bank (HSDB) Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.
Protein Binding 77%
References

[1]. Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. J Clin Oncol. 1986 Mar;4(3):425-39.

[2]. Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity. PLoS One. 2016 Jun 10;11(6):e0156643.

[3]. Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. Pol J Pharmacol, 2004. 56(4): p. 435-44.

[4]. Drugs ten years later: epirubicin. Ann Oncol, 1993. 4(5): p. 359-69.

[5]. Antitumor activity of paclitaxel and epirubicin in human breast carcinoma, R-27. Folia Microbiol (Praha), 1998. 43(5): p. 473-4.

Additional Infomation
Epirubicin Hydrochloride is the hydrochloride salt of the 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin. Epirubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation.
An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.
See also: Epirubicin (has active moiety).
4'-epidoxorubicin is an anthracycline that is the 4'-epi-isomer of doxorubicin. It has a role as an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, an antineoplastic agent and an antimicrobial agent. It is an anthracycline, a deoxy hexoside, an anthracycline antibiotic, an aminoglycoside, a monosaccharide derivative, a member of p-quinones, a primary alpha-hydroxy ketone and a tertiary alpha-hydroxy ketone. It is functionally related to a doxorubicin. It is a conjugate acid of a 4'-epidoxorubicinium.
An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.
Epirubicin is an Anthracycline Topoisomerase Inhibitor. The mechanism of action of epirubicin is as a Topoisomerase Inhibitor.
Epirubicin has been reported in Bos taurus, Lasiodiplodia theobromae, and other organisms with data available.
Epirubicin is a 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin. Epirubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation.
Epirubicin is only found in individuals that have used or taken this drug. It is an anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.
See also: Epirubicin Hydrochloride (has salt form).
Drug Indication
For use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.
FDA Label
Mechanism of Action
Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
Epirubicin is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical and biological functions within eukaryotic cells, the precise mechanisms of epirubicin's cytotoxic and/or antiproliferative properties have not been completely elucidated. Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis. Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to result from these or other possible mechanisms.
Epirubicin fights cancer through topoisomerase II inhibition, hence producing DNA strand breaks that finally lead to cell apoptosis. But anthracyclines produce free radicals that may explain their adverse effects. Dexrazoxane--an iron chelator--was proven to decrease free radical production and anthracycline cardiotoxicity. In this article, we report the concentrations of cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) relative to 2'-deoxyguanosine (dGuo), and comet assay results from a study including 20 cancer patients treated with epirubicin. Plasma concentrations of vitamins A, E, C and carotenoids are also reported. All data were obtained before and immediately after epirubicin infusion. The ratios of 8-Oxo-dGuo to dGuo were measured in leukocyte DNA by HPLC-coulometry after NaI extraction of nucleic acids. Vitamins A and E and carotenoids were measured by HPLC-spectrophotometry. Vitamin C was measured by HPLC-spectrofluorimetry. Median 8-oxo-dGuo/dGuo ratios increased significantly from 0.34 to 0.48 lesions per 100,000 bases while per cent of tail DNA increased from 3.47 to 3.94 after chemotherapy 8-Oxo-dGuo/dGuo and per cent of tail DNA medians remained in the normal range. Only vitamin C decreased significantly from 55.4 to 50.3 microM Decreases in vitamins A, E, lutein and zeaxanthin were not significant, but concentrations were below the lower limit of the normal range both before and after chemotherapy. Only the correlation between comet assay results and vitamin C concentrations was significant (rho =-0.517, p = 0.023). This study shows that cellular DNA is damaged by epirubicin-generated free radicals which produce the mutagenic modified base 8-oxo-dGuo and are responsible for strand breaks. However, strand breaks are created not only by free radicals but also by topoisomerase II inhibition. In a previous study we did not find any significant change in urinary 8-oxo-dGuo excretion after adriamycin treatment. However, 8-oxo-dGuo may have increased at the end of urine collection as DNA repair and subsequent kidney elimination are relatively slow processes. In another study, authors used GC-MS to detect 8-oxo-dGuo in DNA and did not find any change after prolonged adriamycin infusion. Reasons for these apparent discrepancies are discussed.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C27H30CLNO11.HCL
Molecular Weight
579.98
Exact Mass
579.15
Elemental Analysis
C, 55.91; H, 5.21; Cl, 6.11; N, 2.42; O, 30.34
CAS #
56390-09-1
Related CAS #
56390-09-1(HCl salt); 56420-45-2
PubChem CID
65348
Appearance
Red solid powder
Density
1.61g/cm3
Boiling Point
810.3ºC at 760 mmHg
Melting Point
185ºC dec
Flash Point
443.8ºC
Index of Refraction
1.709
LogP
1.503
Hydrogen Bond Donor Count
7
Hydrogen Bond Acceptor Count
12
Rotatable Bond Count
5
Heavy Atom Count
40
Complexity
977
Defined Atom Stereocenter Count
6
SMILES
Cl[H].O([C@@]1([H])C([H])([H])[C@]([H])([C@]([H])(C([H])(C([H])([H])[H])O1)O[H])N([H])[H])[C@]1([H])C2C(=C3C(C4C(=C([H])C([H])=C([H])C=4C(C3=C(C=2C([H])([H])[C@@](C(C([H])([H])O[H])=O)(C1([H])[H])O[H])O[H])=O)OC([H])([H])[H])=O)O[H]
InChi Key
MWWSFMDVAYGXBV-FGBSZODSSA-N
InChi Code
InChI=1S/C27H29NO11.ClH/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34;/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3;1H/t10-,13-,15-,17-,22-,27-;/m0./s1
Chemical Name
(7S,9S)-7-[(2R,4S,5R,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;hydrochloride
Synonyms
4'-epidoxorubicin HCl; 4'-Epidoxorubicin hydrochloride; IMI28; 4-epi DX; EPI; epi DX; 4-epiadriamycin; 4-epidoxorubicin; 4-epidoxorubicin HCl; epiADR; epidoxorubicin; epidorubicin; IMI 28; IMI-28; brand name: Ellence; Pharmorubicin PFS; Pharmorubicin; Farmorubicin; Farmorubicina; Epirubitec;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 25~100 mg/mL (43.1~172.4 mM)
Water: ~100 mg/mL (~172.4 mM)
Ethanol: <1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.31 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (4.31 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.


Solubility in Formulation 4: ≥ 0.5 mg/mL (0.86 mM) (saturation unknown) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 5: 1.1 mg/mL (1.90 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.7242 mL 8.6210 mL 17.2420 mL
5 mM 0.3448 mL 1.7242 mL 3.4484 mL
10 mM 0.1724 mL 0.8621 mL 1.7242 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
Neoadjuvant Dose-dense EC Followed by ABX With PD-1 for Triple Negative Breast Cancer Patients
CTID: NCT04418154
Phase: Phase 2    Status: Active, not recruiting
Date: 2024-05-21
Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer
CTID: NCT00433420
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-05-08
Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma
CTID: NCT00005584
Phase: Phase 3    Status: Active, not recruiting
Date: 2024-02-22
Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer
CTID: NCT00630032
Phase: Phase 3    Status: Completed
Date: 2024-02-21
Capecitabine, Epirubicin, and Carboplatin in Treating Patients With Progressive, Unresectable, or Metastatic Cancer
CTID: NCT00486356
Phase: Phase 1    Status: Completed
Date: 2024-01-03
View More

Dalpiciclib Plus AI (Neoadjuvant Endocrine Therapy) Compared With Neoadjuvant Chemotherapy in Early Breast Cancer (EBC)
CTID: NCT06107673
Phase: Phase 2    Status: Recruiting
Date: 2023-10-30


Comparison of SEEOX and SOX Regimens in Stage ⅢB/ⅢC Gastric Cancer Patients
CTID: NCT02338518
Phase: Phase 3    Status: Active, not recruiting
Date: 2023-09-29
Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer
CTID: NCT00066443
Phase: Phase 1/Phase 2    Status: Completed
Date: 2023-08-04
Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer
CTID: NCT02315196
Phase: Phase 2    Status: Active, not recruiting
Date: 2023-03-29
Sorafenib Tosylate, Combination Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With High-Risk Stage IIB-IV Soft Tissue Sarcoma
CTID: NCT02050919
Phase: Phase 2    Status: Completed
Date: 2022-03-21
A Phase 3 Study to Evaluate the Safety and Efficacy of APL-1202 as a Single-agent Oral Treatment Versus Intravesical Instillation of Epirubicin Hydrochloride in naïve Intermediate-risk NMIBC Patients
CTID: NCT04736394
Phase: Phase 3    Status: Recruiting
Date: 2022-02-22
Combination Chemotherapy in Treating Patients With Extensive Stage Small Cell Lung Cancer
CTID: NCT00003606
Phase: Phase 3    Status: Completed
Date: 2021-02-21
Combination Chemotherapy With or Without Colony-stimulating Factors in Treating Women With Breast Cancer
CTID: NCT00014222
Phase: Phase 3    Status: Completed
Date: 2020-10-05
Epirubicin in Treating Women Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Breast Cancer
CTID: NCT00253500
Phase: Phase 2    Status: Completed
Date: 2020-07-24
Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer
CTID: NCT00052910
Phase: Phase 3    Status: Completed
Date: 2020-05-07
Docetaxel and Epirubicin With and Without G-CSF in Treating Women With Metastatic Breast Cancer
CTID: NCT00002866
Phase: Phase 1    Status: Completed
Date: 2020-04-01
Tamoxifen in Treating Women With High-Risk Breast Cancer
CTID: NCT00002542
Phase: Phase 3    Status: Completed
Date: 2020-04-01
Efficacy and Tolerance Study of Bevacizumab in Her2- Inflammatory Breast Cancer Patients
CTID: NCT00820547
Phase: Phase 2    Status: Completed
Date: 2019-10-22
A Study of Bortezomib Combined With CHEP in Peripheral T Cell Lymphoma
CTID: NCT04061772
Phase: Phase 2    Status: Unknown status
Date: 2019-08-20
Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach
CTID: NCT00601705
Phase: Phase 2    Status: Completed
Date: 2019-04-30
Breast Cancer Treatment Based on Organ-like Culture
CTID: NCT03925233
Phase:    Status: Unknown status
Date: 2019-04-24
Combination Therapy of Anthracyclines for Children With Nephroblastoma
CTID: NCT03892330
Phase: Phase 4    Status: Not yet recruiting
Date: 2019-03-27
Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery
CTID: NCT00513292
Phase: Phase 3    Status: Completed
Date: 2019-01-23
Sorafenib, Epirubicin, Ifosfamide, and Radiation Therapy Followed By Surgery in Treating Patients With High-Risk Stage II or Stage III Soft Tissue Sarcoma
CTID: NCT00822848
Phase: Phase 1    Status: Completed
Date: 2018-09-07
Combination Chemotherapy in Treating Patients With Early Stage Breast Cancer That Has Been Removed By Surgery
CTID: NCT00301925
Phase: Phase 3    Status: Unknown status
Date: 2018-08-08
Epirubicin and Docetaxel in Treating Patients With Metastatic Prostate Cancer
CTID: NCT00096304
Phase: Phase 1    Status: Terminated
Date: 2018-04-10
Dinaciclib and Epirubicin Hydrochloride in Treating Patients With Metastatic Triple-Negative Breast Cancer
CTID: NCT01624441
Phase: Phase 1    Status: Completed
Date: 2018-03-30
Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors
CTID: NCT00878904
Phase: Phase 1    Status: Completed
Date: 2017-03-24
Gemcitabine and Epirubicin in Treating Patients With Malignant Mesothelioma
CTID: NCT00017186
Phase: Phase 2    Status: Completed
Date: 2016-12-07
Epirubicin Hydrochloride, Cisplatin, and Fluorouracil or Capecitabine With or Without Lapatinib Ditosylate as First-Line Therapy in Treating Patients With Stomach Cancer or Gastroesophageal Junction Cancer
CTID: NCT01123473
Phase: Phase 2    Status: Terminated
Date: 2016-10-12
Epirubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab in Treating Women With HER2-Positive Stage III or Stage IV Breast Cancer
CTID: NCT00379015
Phase: Phase 2    Status: Completed
Date: 2016-09-28
Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors
CTID: NCT00003852
Phase: Phase 2    Status: Terminated
Date: 2016-06-23
Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30
CTID: NCT00753207
Phase: Phase 1    Status: Completed
Date: 2016-02-15
Radiation Therapy and Docetaxel Followed by Standard Therapy in Treating Women With Breast Cancer
CTID: NCT00872625
Phase: Phase 1    Status: Completed
Date: 2015-02-10
Sulindac and Epirubicin in Treating Patients With Metastatic Malignant Melanoma
CTID: NCT00755976
Phase: Phase 2    Status: Completed
Date: 2014-12-31
High Dose Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Therapy in Treating Women With Locally Recurrent or Metastatic Breast Cancer
CTID: NCT00002870
Phase: Phase 3    Status: Completed
Date: 2014-12-16
Combination Chemotherapy Compared With Observation After Surgery in Treating Women With Relapsed Nonmetastatic Breast Cancer
CTID: NCT00053911
Phase: Phase 3    Status: Terminated
Date: 2014-12-16
Adjuvant Chemotherapy Plus Radiation Therapy in Treating Women With Early-Stage Breast Cancer
CTID: NCT00003893
Phase: Phase 3    Status: Completed
Date: 2013-12-19
Surgery With or Without Combination Chemotherapy in Treating Patients With Stomach Cancer
CTID: NCT00002615
Phase: Phase 3    Status: Completed
Date: 2013-12-19
Combination Chemotherapy With or Without Epirubicin in Treating Women With Stage I or Stage II Breast Cancer
CTID: NCT00003577
Phase: Phase 3    Status: Completed
Date: 2013-12-19
Combination Chemotherapy in Treating Women With Stage II or Stage III Breast Cancer
CTID: NCT00005581
Phase: Phase 3    Status: Unknown status
Date: 2013-12-18
Epirubicin and Tamoxifen With or Without Docetaxel in Treating Postmenopausal Women With Breast Cancer
CTID: NCT00010140
Phase: Phase 3    Status: Unknown status
Date: 2013-12-18
Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma
CTID: NCT00002898
Phase: Phase 3    Status: Completed
Date: 2013-12-04
Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors
CTID: NCT00025441
Phase: Phase 2    Status: Completed
Date: 2013-12-04
Epirubicin and Cyclophosphamide Compared With Epirubicin and Paclitaxel in Treating Women With Metastatic Breast Cancer
CTID: NCT00002953
Phase: Phase 3    Status: Completed
Date: 2013-12-04
Combination Chemotherapy Following Surgery in Treating Women With Early Stage Breast Cancer
CTID: NCT00003012
Phase: Phase 3    Status: Completed
Date: 2013-11-06
Comparison of Three Combination Chemotherapy Regimens in Treating Women With Stage I or Stage II Breast Cancer
CTID: NCT00004237
Phase: Phase 2    Status: Completed
Date: 2013-11-06
B
A Randomized Placebo controlled Phase I/II Study Evaluating the Safety and Efficacy of Alpha1H in adult patients with non-muscle invasive bladder cancer awaiting transurethral surgery
CTID: null
Phase: Phase 1, Phase 2    Status: Ongoing
Date: 2018-05-07
Effects of Identifying and Treating Early, Subclinical Cardiotoxicity on the Long- Term Incidence of Clinical Cardiotoxicity in Women with Breast Cancer, a prospective randomised study: The Cardio-Oncology Breast Cancer Study.
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2017-08-19
Predictive value of in-vitro testing anti-cancer therapy sensitivity on tumorspheres from patients with metastatic colorectal cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2017-07-10
Tocotrienol in combination with neoadjuvant chemotherapy for women with breast cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2016-07-21
A prospective, Belgian multi-center, single-arm, phase II study of neoadjuvant weekly paclitaxel and carboplatin followed by dose dense epirubicin and cyclophosphamide in stage II and III triple negative breast cancer.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2015-05-27
Molecular-biological tumor profiling for drug treatment selection in patients with advanced and refractory carcinoma
CTID: null
Phase: Phase 2    Status: Completed
Date: 2015-05-04
A phase II randomized, open-label neo-adjuvant study of standard chemotherapy regimen compared to high dose chemotherapy regimen with autologous stem cell transplantation in patients with triple negative breast cancer
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2015-04-20
Response to Optimal Selection of neo-adjuvant Chemotherapy in Operable breast cancer: A randomised phase III, stratified biomarker trial of neo-adjuvant 5-Fluorouracil, Epirubicin and Cyclophosphamide vs Docetaxel and Cyclophosphamide chemotherapy
CTID: null
Phase: Phase 3    Status: GB - no longer in EU/EEA
Date: 2015-01-08
A randomized phase III trial comparing two dose-dense, dose-intensified approaches (ETC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto)
CTID: null
Phase: Phase 3    Status: Completed
Date: 2014-11-04
Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction
CTID: null
Phase: Phase 2    Status: Completed
Date: 2014-04-22
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled Study of Rilotumumab (AMG 102) with Epirubicin, Cisplatin, and Capecitabine (ECX) as First-line Therapy in Advanced MET-Positive Gastric or Gastroesophageal Junction Adenocarcinoma
CTID: null
Phase: Phase 3    Status: Prematurely Ended, Completed
Date: 2012-12-11
A Randomized Phase III Study Of Low-Docetaxel Oxaliplatin, Capecitabine (Low-Tox) Vs Epirubicin, Oxaliplatin And Capecitabine (Eox) In Patients With Locally Advanced Unresectable Or Metastatic Gastric Cancer
CTID: null
Phase: Phase 3    Status: Prematurely Ended
Date: 2012-04-18
“ESTUDIO FASE II MULTINACIONAL, MULTICÉNTRICO,PARA EVALUAR LA SEGURIDAD CLÍNICA Y VIABILIDAD DE LA ADMINISTRACIÓN DE T-DM1 DE FORMA SECUENCIAL CON UN RÉGIMEN DE QUIMIOTERAPIA BASADO EN ANTRACICLINAS, PARA EL TRATAMIENTO ADYUVANTE O NEOADYUVANTE DE PACIENTES CON CÁNCER DE MAMA HER2 POSITIVO PRECOZ”
CTID: null
Phase: Phase 2    Status: Completed
Date: 2010-10-18
Randomized, fase II-III study of peri and post surgery chemiotherapy in removable pancreas carcinoma
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2010-07-02
Neoadjuvant, sequential chemotherapy with docetaxel followed by Fluorouracil, Epirubicin, and Cyclophosphamid every 3 weeks - genome wide expression analysis for identification of a predictive gene signature in patients with primary breast cancer
CTID: null
Phase: Phase 2    Status: Completed
Date: 2009-11-12
Proteomic profile analysis to classify advanced pancreatic adenocarcinoma patients for clinical outcome after treatment with PDXG (cisplatin, docetaxel, capecitabine, gemcitabine) or PEXG (cisplatin, epirubicin, capecitabine, gemcitabine) regimen.
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2009-07-07
Populationsbaseret farmakokinetisk og farmakodynamisk doseringsmodel af epirubicin, cyklofosfamid og docetaxel til brystkræft
CTID: null
Phase: Phase 4    Status: Prematurely Ended
Date: 2009-05-29
PHASE II TRIAL OF PRIMARY CHEMOTHERAPY WITH TRASTUZUMAB IN COMBINATION WITH DOCETAXEL FOLLOWED BY EPIRUBICIN-CYCLOPHOSPHAMIDE IN PATIENTS WITH HER2-OVEREXPRESSING OPERABLE BREAST CANCER
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2009-01-15
Phase-IIb-Study to Evaluate the Effect of a Neoadjuvant Chemotherapy with Docetaxel, Epirubicine and Cyclphosphamide (TEC) in Patients with primary HER-2 neu Negative Mammacarcinoma
CTID: null
Phase: Phase 2    Status: Completed
Date: 2008-12-30
Simultaneous Study of Docetaxel Based Anthracycline Free
CTID: null
Phase: Phase 3    Status: Completed
Date: 2008-12-17
NEOADJUVANT EPIRUBICIN-OXALIPLATIN-XELODA AND OXALIPLATIN-XELODA-RADIOTHERAPY IN LOCALLY ADVANCED, RESECTABLE, GASTRIC CANCER. A PHASE II COLLABORATIVE STUDY
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2008-11-02
A multi-centre phase II trial to assess the efficacy of epirubicin, cisplatin and capecitabine incorporating the prospective validation of molecular classifiers and exploratory metabonomics.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2008-10-08
Randomized trial of sequential epirubicin and docetaxel against docetaxel in patients with early operable breast cancer.
CTID: null
Phase: Phase 3    Status: Completed
Date: 2008-05-06
Preoperative treatment of breast cancer with a combination of epirubicin, docetaxel and bevacizumab. A translational trial on molecular markers and functional imaging to predict response early
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2008-03-12
A neoadjuvant study of chemotherapy versus endocrine therapy in postmenopausal patients with primary breast cancer
CTID: null
Phase: Phase 3    Status: Completed
Date: 2008-01-28
Study of Radioembolization (RE) with SIR-Spheres® versus Transarterial Chemoembolisation (TACE) in patients with unresectable primary Hepatocellular Carcinoma. A comparative, prospective, randomised, open, pilot trial to evaluate health-related quality of life, pharmaco-economic parameters, and efficacy.
CTID: null
Phase: Phase 4    Status: Completed
Date: 2007-07-16
PHASE II TRIAL OF THE MULTI-DRUG RESISTANCE PROTEIN MODULATING AGENT SULINDAC IN COMBINATION WITH EPIRUBICIN IN PATIENTS WITH ADVANCED MELANOMA
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2007-04-04
A phase I-II study of lapatinib and docetaxel as neoadjuvant treatment for HER-2 positive locally advanced/inflammatory or large operable breast cancer.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2007-01-15
ESTUDIO MULTICÉNTRICO FASE II DE DISTRIBUCIÓN ALEATORIA, PARA EVALUAR LA EFICACIA DE TRATAMIENTO NEOADYUVANTE SELECTIVO SEGÚN SUBTIPO INMUNOHISTOQUÍMICO EN CÁNCER DE MAMA HER2 NEGATIVO
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2006-12-01
A multicenter randomized phase III trial of neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy in resectable gastric cancer (CRITICS-study: ChemoRadiotherapy after Induction chemoTherapy In Cancer of the Stomach)
CTID: null
Phase: Phase 3    Status: Ongoing, Completed
Date: 2006-10-17
Dose-dense treatment with gemcitabine, epirubicin and paclitaxel GET combination in advanced breast cancer a phase II parallel study
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2006-07-11
Neoadjuvant treatment in high risk superficial soft tissue sarcomas of limbs and soft tissue of the trunk phase II study
CTID: null
Phase: Phase 2    Status: Prematurely Ended
Date: 2006-05-03
Observational pharmacokinetic study of doxorubicin and cyclophosphamide in patients with early breast cancer.
CTID: null
Phase: Phase 4    Status: GB - no longer in EU/EEA
Date: 2006-03-07
VINORELBINE CAPECITABINE EPIRUBICINE AS FIRST LINE THERAPY IN ADVANCED BREAST CANCER PATIENTS
CTID: null
Phase: Phase 2    Status: Ongoing
Date: 2006-02-22
Evaluation of Response Rate to Pre-operative Docetaxel + Herceptin study part A and Docetaxel study part B In Locally Advanced Breast Cancer Patients, Stratified by HER2-Status, Trial Phase II
CTID: null
Phase: Phase 2    Status: Completed
Date: 2005-12-30
PEXG VERSUS PDXG IN LOCALLY ADVANCED OR METASTATIC PANCREATIC ADENOCARCINOMA : RANDOMIZED, PHASE II STUDY.
CTID: null
Phase: Phase 2    Status: Completed
Date: 2005-07-01
Randomized clinical trial to evaluate the predictive accuracy of a gene
CTID: null
Phase: Phase 4    Status: Ongoing
Date: 2005-06-01

Biological Data
  • Epirubicin (EPI) represses the inhibitory effect of Foxp3 on the activity of NF-κB. PLoS One . 2016 Jun 10;11(6):e0156643.
  • Epirubicin (EPI) blocks the physical interaction between Foxp3 and the p65 subunit of NF-κB. PLoS One . 2016 Jun 10;11(6):e0156643.
  • Epirubicin (EPI) inhibits the immunosuppressive activity of murine Tregs in vitro. PLoS One . 2016 Jun 10;11(6):e0156643.
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