Etoposide

Approved Indications:

• Small Cell Lung Cancer (SCLC): Treatment of limited or extensive-stage small cell lung carcinoma.
• Testicular Cancer: Part of combination chemotherapy regimens for metastatic testicular tumors.
• Lymphomas: Hodgkin's lymphoma and non-Hodgkin's lymphoma, as part of combination chemotherapy.
• Acute Myeloid Leukemia (AML): Used in combination regimens for induction therapy.
• Germ Cell Tumors: Treatment of germ cell tumors resistant or recurrent to first-line therapy.
• Other Solid Tumors: Ovarian cancer, cervical cancer, and neuroblastoma as part of multi-agent chemotherapy protocols.

Off-label / Clinically Accepted Uses:

• Treatment of refractory or relapsed cancers where standard therapies fail.
• Use in conditioning regimens for hematopoietic stem cell transplantation.

Routes: Intravenous (IV) infusion or oral administration.

IV Administration:

• Adult dosing (e.g., for SCLC): 100 mg/m² IV over 30 to 60 minutes daily for 3 consecutive days every 3 to 4 weeks.
• Dose adjustments based on hematologic tolerance.
• Infusion rates should not exceed 60 minutes to reduce risk of hypotension.

Oral Administration:

• Typical dose: 200 mg/m² per day for 5 days every 3 to 4 weeks.
• Administer on an empty stomach; avoid food 1 hour before and after dosing to optimize absorption.
• Capsules should be swallowed whole with water.

Special Populations:

• Pediatrics: Dosing varies by indication and body surface area; generally similar mg/m²-based regimens.
• Elderly: Dose adjustment may be necessary based on organ function and tolerance.
• Renal Impairment: Caution advised; no formal dose adjustment but monitor closely.
• Hepatic Impairment: Dose reduction recommended if bilirubin elevated; detailed adjustment based on levels.

Etoposide is a topoisomerase II inhibitor that stabilizes the DNA-topoisomerase II complex during DNA replication. By preventing the relegation of double-stranded DNA breaks induced by topoisomerase II, etoposide causes accumulation of DNA breaks leading to cell cycle arrest in the S and G2 phases, and ultimately induces apoptosis of rapidly dividing cancer cells.

• Absorption: Oral bioavailability approximately 50%, variable; IV administration bypasses absorption.
• Distribution: Widely distributed with volume of distribution ~20 L/m²; plasma protein binding 94%.
• Metabolism: Hepatic metabolism mainly via CYP3A4 enzymes; formation of inactive metabolites.
• Elimination Half-life: Approximately 4 to 11 hours; variable with renal and hepatic function.
• Excretion: Approximately 40–60% excreted renally; remainder via feces.

• Pregnancy: Classified as FDA Category D (positive evidence of human fetal risk). Use only if benefits outweigh risks.
• Lactation: Excreted in breast milk; breastfeeding is not recommended during treatment due to potential toxicity to the infant.

• Primary Class: Antineoplastic Agent
• Subclass: Topoisomerase II inhibitor; Cytotoxic chemotherapy

• Known hypersensitivity to etoposide or formulation components.
• Severely impaired bone marrow function.
• Severe hepatic impairment without appropriate dose adjustment.
• Concomitant use with other agents causing severe myelosuppression without close monitoring.

• Myelosuppression: Severe neutropenia and thrombocytopenia requiring frequent blood count monitoring.
• Hypersensitivity Reactions: Infusion-related reactions including hypotension and anaphylaxis.
• Secondary Leukemia: Risk of treatment-related acute myeloid leukemia/myelodysplastic syndrome.
• Pregnancy and Fertility: Teratogenic and gonadotoxic; advise contraception during and post-treatment.
• Infusion-related Hypotension: Slow infusion rates recommended.
• Hepatic and Renal Dysfunction: Dose modification necessary; careful monitoring required.
• Mucositis: Monitor and manage oral and gastrointestinal mucosal toxicity.

Common Adverse Effects:

• Hematologic: Neutropenia, thrombocytopenia, anemia.
• Gastrointestinal: Nausea, vomiting, diarrhea, mucositis.
• Alopecia.
• Fatigue, malaise.

Serious/Rare Side Effects:

• Hypotension during infusion.
• Severe hypersensitivity reactions.
• Secondary leukemia (especially with prolonged use).
• Hepatotoxicity.
• Infertility and gonadal suppression.

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): Increase etoposide plasma concentration, enhancing toxicity risk.
• CYP3A4 inducers (e.g., rifampin, phenytoin): Reduce etoposide levels, potentially decreasing efficacy.
• Other myelosuppressive agents: Additive hematologic toxicity.
• Warfarin: Potential enhanced anticoagulant effect; monitor INR closely.

• Recent oncology guidelines continue to recommend etoposide as a key component in treatment regimens for SCLC, testicular cancer, and lymphomas.
• Emphasis on early recognition and management of infusion reactions.
• Recommendations on dose adjustments in hepatic impairment updated to improve safety.
• No new major safety warnings but ongoing monitoring of secondary leukemia risk advised.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light.
• Keep vial tightly closed.
• For IV formulations, reconstituted solutions should be used promptly or stored refrigerated as per manufacturer instructions.
• Keep out of reach of children.