Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Epirubicin Hcl

Epirubicin Hcl

Epirubicin Hydrochloride: A Comprehensive Review of Its Role in Chemotherapy

Introduction

Epirubicin Hydrochloride (Epirubicin HCl) is a potent anthracycline chemotherapeutic agent widely used in the treatment of various malignancies, including breast cancer, gastric cancer, lung cancer, and hematologic malignancies. As a derivative of doxorubicin, epirubicin offers a better safety profile, particularly in terms of reduced cardiotoxicity, making it a preferred option in many oncology protocols.

Chemical and Pharmacological Profile

  • Chemical Name: (8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-8-glycoloyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione hydrochloride

  • Molecular Formula: C27H29NO11·HCl

  • Molecular Weight: 579.99 g/mol

  • Drug Class: Anthracycline antibiotic, antineoplastic agent

  • ATC Code: L01DB03

Epirubicin is structurally similar to doxorubicin but differs in its stereochemistry, which contributes to its altered metabolism and reduced cardiotoxicity.

Mechanism of Action

Epirubicin’s antitumor effects stem from multiple mechanisms:

1. DNA Intercalation and Inhibition of Topoisomerase II

  • Epirubicin intercalates (inserts) into DNA strands, disrupting normal DNA replication and transcription.

  • It inhibits topoisomerase II, an enzyme crucial for DNA unwinding, leading to double-strand breaks and apoptosis (programmed cell death).

2. Generation of Free Radicals

  • Epirubicin undergoes redox cycling, generating reactive oxygen species (ROS), which cause oxidative damage to cancer cells.

3. Apoptosis Induction

  • Epirubicin activates p53-dependent pathways, promoting cell cycle arrest and apoptosis in tumor cells.

These multiple cytotoxic effects make Epirubicin highly effective against rapidly proliferating cancer cells.

Pharmacokinetics

  • Absorption: Epirubicin is administered intravenously (IV); it is not suitable for oral administration.

  • Distribution: Rapidly distributed to tissues, especially in highly perfused organs (liver, heart, kidneys).

  • Metabolism: Primarily metabolized in the liver via glucuronidation.

  • Half-life: 30–40 hours (triphasic elimination).

  • Excretion: Eliminated through bile (75%) and urine (10–15%).

Unlike doxorubicin, epirubicin's rapid hepatic metabolism reduces cardiac accumulation, lowering the risk of chronic cardiotoxicity.

Therapeutic Indications

Epirubicin is an important chemotherapeutic agent in the treatment of various cancers, including:

1. Breast Cancer (Primary Indication)

  • Used as neoadjuvant (pre-surgical) and adjuvant (post-surgical) therapy.

  • Commonly combined with cyclophosphamide and 5-fluorouracil (FEC regimen).

2. Gastric Cancer

  • Part of combination chemotherapy (e.g., ECF regimen: Epirubicin + Cisplatin + 5-Fluorouracil).

3. Lung Cancer

  • Effective in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).

  • Used in combination regimens such as EP (Epirubicin + Cisplatin).

4. Ovarian Cancer

  • Sometimes included in platinum-based regimens for advanced ovarian cancer.

5. Bladder Cancer

  • Used as intravesical chemotherapy to reduce recurrence rates in superficial bladder cancer.

6. Hematologic Malignancies

  • Utilized in acute myeloid leukemia (AML) and lymphomas.

Clinical Efficacy and Trials

Breast Cancer Studies

  • NSABP B-15 Trial: Compared epirubicin-based therapy to doxorubicin in node-positive breast cancer, showing similar efficacy but reduced cardiotoxicity.

  • FE100C vs. AC Regimen Study: Found that Epirubicin-based FEC chemotherapy was superior to doxorubicin + cyclophosphamide (AC) in disease-free survival.

Gastric Cancer Studies

  • MAGIC Trial: Showed that ECF (Epirubicin, Cisplatin, 5-FU) improved survival rates in resectable gastric cancer.

These studies underscore Epirubicin’s efficacy in solid tumors, with an improved safety profile compared to doxorubicin.

Dosage and Administration

IV Administration:

  • Breast Cancer: 100–120 mg/m² every 3 weeks (as monotherapy or in combination).

  • Gastric Cancer: 50 mg/m² Day 1 every 3 weeks (as part of ECF).

  • Bladder Cancer (Intravesical): 50 mg instilled directly into the bladder.

Duration: Typically 6 cycles, but may vary based on response and toxicity.

Dose Modifications

  • Hepatic Impairment: Dose reduction required.

  • Renal Impairment: Caution in severe kidney disease.

  • Elderly Patients: Consider reduced doses.

Adverse Effects

Common Side Effects

  • Nausea and vomiting

  • Alopecia (hair loss)

  • Fatigue

  • Myelosuppression (low blood counts)

Severe Side Effects

  • Cardiotoxicity: Can cause congestive heart failure (CHF) at high cumulative doses (>900 mg/m²).

  • Secondary Leukemia: Long-term risk.

  • Hepatotoxicity: Elevated liver enzymes.

  • Mucositis: Oral ulcers.

To mitigate cardiotoxicity, monitoring ejection fraction (LVEF) via echocardiography is recommended.

Contraindications

  • Severe cardiac dysfunction (e.g., recent myocardial infarction, heart failure).

  • Severe hepatic impairment.

  • Persistent severe neutropenia.

  • Pregnancy and lactation.

Due to its teratogenic potential, Epirubicin should not be used in pregnant women unless absolutely necessary.

Drug Interactions

  • Increased Toxicity with Trastuzumab: Higher cardiotoxic risk.

  • Increased Bone Marrow Suppression: When combined with paclitaxel or cisplatin.

  • CYP3A4 Inhibitors (e.g., Ketoconazole) may increase Epirubicin levels.

Patients should avoid alcohol and hepatotoxic drugs during treatment.

Comparison with Other Anthracyclines

Drug Cardiotoxicity Half-life Main Use
Epirubicin Lower 30-40 hrs Breast, gastric cancer
Doxorubicin Higher 20-48 hrs Breast, lymphomas
Daunorubicin Moderate 18-26 hrs Leukemia
Idarubicin Low 22-26 hrs Leukemia

Epirubicin's favorable safety profile makes it the preferred choice in many protocols.

Future Research and Innovations

  • Nanoparticle and liposomal formulations to further reduce toxicity.

  • Combination with immunotherapy (PD-1 inhibitors) for enhanced efficacy.

  • Genetic profiling to personalize dosing based on patient metabolism.

Conclusion

Epirubicin remains a cornerstone of modern chemotherapy, particularly in breast and gastric cancers, due to its potent anticancer effects and improved cardiac safety profile. Ongoing research aims to further optimize its use, making it a valuable tool in oncology for years to come.

Avaiable Medicines