Epirubicin is an anthracycline cytotoxic agent, is a 4'-epi-isomer of doxorubicin. The compound is marketed by Pfizer under the trade name Ellence in the US. It is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer. 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. It is known, that 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.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | ELLENCE Approved UseEpirubicin Hydrochloride Injection is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer Launch Date1999 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.7 μg/mL |
60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.3 μg/mL |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.6 μg × h/mL |
60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.2 μg × h/mL |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
35.3 h |
60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
31.1 h |
150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
23% |
60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
EPIRUBICIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: Page: p.13,14 |
unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: Page: p.13,14 |
DLT: Thrombocytopenia, Leukopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 67%) Sources: Page: p.13,14Leukopenia (grade 4, 67%) Myelosuppression (grade 4, 100%) Stomatitis (grade 3, 33%) |
95 mg/m2 1 times / day multiple, intravenous Overdose Dose: 95 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 95 mg/m2, 1 times / day Sources: Page: p.11 |
unhealthy, 36 n = 1 Health Status: unhealthy Condition: non-Hodgkin’s lymphoma Age Group: 36 Sex: M Population Size: 1 Sources: Page: p.11 |
Disc. AE: Aplasia bone marrow, Mucositis... AEs leading to discontinuation/dose reduction: Aplasia bone marrow Sources: Page: p.11Mucositis (grade 4) Gastrointestinal bleeding |
320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
Disc. AE: Hyperthermia, Multiple organ failure... AEs leading to discontinuation/dose reduction: Hyperthermia Sources: Page: p.11Multiple organ failure Lactic acidosis Lactate dehydrogenase increased Anuria |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
Disc. AE: Soft tissue necrosis... AEs leading to discontinuation/dose reduction: Soft tissue necrosis (severe) Sources: Page: p.1 |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
DLT: Leukopenia, Neutropenia... Disc. AE: Toxic myocarditis, Congestive heart failure... Dose limiting toxicities: Leukopenia AEs leading toNeutropenia discontinuation/dose reduction: Toxic myocarditis (severe) Sources: Page: p.1Congestive heart failure (grade 3-5) Acute promyelocytic leukemia Myelosuppression (severe) Hyperuricemia Thrombophlebitis Thromboembolic event Pulmonary embolism |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Stomatitis | grade 3, 33% DLT, Disc. AE |
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: Page: p.13,14 |
unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: Page: p.13,14 |
| Myelosuppression | grade 4, 100% DLT, Disc. AE |
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: Page: p.13,14 |
unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: Page: p.13,14 |
| Leukopenia | grade 4, 67% DLT, Disc. AE |
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: Page: p.13,14 |
unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: Page: p.13,14 |
| Thrombocytopenia | grade 4, 67% DLT, Disc. AE |
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: Page: p.13,14 |
unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: Page: p.13,14 |
| Aplasia bone marrow | Disc. AE | 95 mg/m2 1 times / day multiple, intravenous Overdose Dose: 95 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 95 mg/m2, 1 times / day Sources: Page: p.11 |
unhealthy, 36 n = 1 Health Status: unhealthy Condition: non-Hodgkin’s lymphoma Age Group: 36 Sex: M Population Size: 1 Sources: Page: p.11 |
| Gastrointestinal bleeding | Disc. AE | 95 mg/m2 1 times / day multiple, intravenous Overdose Dose: 95 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 95 mg/m2, 1 times / day Sources: Page: p.11 |
unhealthy, 36 n = 1 Health Status: unhealthy Condition: non-Hodgkin’s lymphoma Age Group: 36 Sex: M Population Size: 1 Sources: Page: p.11 |
| Mucositis | grade 4 Disc. AE |
95 mg/m2 1 times / day multiple, intravenous Overdose Dose: 95 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 95 mg/m2, 1 times / day Sources: Page: p.11 |
unhealthy, 36 n = 1 Health Status: unhealthy Condition: non-Hodgkin’s lymphoma Age Group: 36 Sex: M Population Size: 1 Sources: Page: p.11 |
| Anuria | Disc. AE | 320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
| Hyperthermia | Disc. AE | 320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
| Lactate dehydrogenase increased | Disc. AE | 320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
| Lactic acidosis | Disc. AE | 320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
| Multiple organ failure | Disc. AE | 320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: Page: p.11 |
unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: Page: p.11 |
| Soft tissue necrosis | severe Disc. AE |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Leukopenia | DLT, Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Neutropenia | DLT, Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Acute promyelocytic leukemia | Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Hyperuricemia | Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Pulmonary embolism | Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Thromboembolic event | Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Thrombophlebitis | Disc. AE | 120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Congestive heart failure | grade 3-5 Disc. AE |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Myelosuppression | severe Disc. AE |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
| Toxic myocarditis | severe Disc. AE |
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: Page: p.1 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Dose-dense sequential chemotherapy with epirubicin and paclitaxel in advanced breast cancer. | 2001 |
|
| Adjuvant chemotherapy for gastro-oesophageal cancer with epirubicin, cisplatin and fluorouracil: a single-centre experience. | 2001 |
|
| Complete cure of malignant lymphoma of the stomach with a huge adrenal lesion achieved by preoperative chemotherapy and surgery: report of a case. | 2001 |
|
| Intensified chemotherapy supported by DMSO-free peripheral blood progenitor cells in breast cancer patients. | 2001 Apr |
|
| Differential anthracycline sensitivity in two related human colon carcinoma cell lines expressing similar levels of P-glycoprotein. | 2001 Apr 10 |
|
| Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon. | 2001 Feb |
|
| Anthracycline adjuvant chemotherapy: how much is enough? | 2001 Feb 1 |
|
| Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function. | 2001 Jan |
|
| Treatment of classical type Kaposi's sarcoma with paclitaxel. | 2001 Jan-Feb |
|
| Reversal of multidrug resistance to epirubicin by cyclosporin A in liposomes or intralipid. | 2001 Jan-Feb |
|
| Prognostic factors for recurrence in stage II and III gastric cancer patients receiving a curative resection and postoperative adjuvant chemotherapy. | 2001 Jan-Feb |
|
| Activation of caspase-3 in renal cell carcinoma cells by anthracyclines or 5-fluorouracil. | 2001 Jul |
|
| Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting. | 2001 Jun |
|
| Phase II study of epirubicin, mitomycin C, and 5-fluorouracil in hormone-refractory prostatic carcinoma. | 2001 Jun |
|
| Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer. | 2001 Jun |
|
| Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. | 2001 Jun 15 |
|
| Contrast-enhanced subtraction harmonic sonography for evaluating treatment response in patients with hepatocellular carcinoma. | 2001 Mar |
|
| Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3. | 2001 Mar 1 |
|
| Docetaxel and epirubicin plus G-CSF as mobilizing treatment to support high-dose chemotherapy in breast cancer. | 2001 Mar-Apr |
|
| Prophylactic chemolipiodolization for postoperative hepatoma patients. | 2001 Mar-Apr |
|
| Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study. | 2001 May |
|
| Optimizing adjuvant breast cancer chemotherapy: rationale for the MA.21 study. | 2001 May |
|
| New combinations with epirubicin in advanced breast cancer. | 2001 May |
|
| Epirubicin/taxane combinations in breast cancer: experience from several Italian trials. | 2001 May |
|
| Dose-dense and sequential strategies in adjuvant breast cancer therapy. | 2001 May |
|
| Body surface area as a determinant of pharmacokinetics and drug dosing. | 2001 May |
|
| Neoadjuvant chemotherapy for Chinese women with locally advanced breast cancer. | 2001 May |
Sample Use Guides
Injection is administered to patients by intravenous infusion. Drug is given in 14 repeated 3- to 4-week cycles. The total dose may be given on Day 1 of each cycle 15 or divided equally and given on Days 1 and 8 of each cycle. The recommended starting dose is 100 to 120 mg/m2.
Route of Administration:
Intravenous
It was investigated the effect of combined treatment with the anthracycline agent epirubicin (EPI) and NK cells on human breast cancer cells. NK cells were obtained by autologous adoptive cell transfer from breast cancer patients and amplified for 14 days in vitro. The cytotoxicity of NK cells against breast cancer cells was higher following EPI (5.0 μg/ml) pretreatment than without EPI pretreatment or application of EPI alone. The expression of NKG2D ligands [unique long 16-binding protein (ULBP) 1, ULBP2, and major histocompatibility complex class I-related chain A] in breast cancer cells was upregulated by pretreatment with EPI, which also increased the secretion of interferon-γ and tumor necrosis factor-α and expression of perforin and granzyme B in NK cells. These results indicate that EPI-NK cell treatment has synergistic cytotoxic effects against breast cancer cells, and suggest that anthracycline-based chemotherapy and NK cell-based immunotherapy can be combined for more effective breast cancer treatment.
| Substance Class |
Polymer
Created
by
admin
on
Edited
Sat Dec 16 13:26:22 GMT 2023
by
admin
on
Sat Dec 16 13:26:22 GMT 2023
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| Record UNII |
RQU6X0IM9R
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| Record Status |
Validated (UNII)
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| Record Version |
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-
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Code | English | ||
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Common Name | English | ||
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Code | English |
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C139003
Created by
admin on Sat Dec 16 13:26:22 GMT 2023 , Edited by admin on Sat Dec 16 13:26:22 GMT 2023
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PRIMARY | NCIT | ||
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RQU6X0IM9R
Created by
admin on Sat Dec 16 13:26:22 GMT 2023 , Edited by admin on Sat Dec 16 13:26:22 GMT 2023
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| MOL_WEIGHT | CHEMICAL |
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