Drug reference

Etoposide

Antineoplastic

Also known as etoposide phosphate

AntineoplasticATC null

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Avoid (teratogenic in animal studies).

FDA category + note

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Mechanism

Etoposide is a semisynthetic podophyllotoxin derivative that inhibits topoisomerase II by stabilizing the enzyme-DNA cleavable complex, preventing religation of double-strand DNA breaks. Unlike its parent compound podophyllotoxin (which inhibits tubulin), etoposide does not affect microtubule assembly. It is cell-cycle specific, with maximal cytotoxicity in the late S and G2 phases. Etoposide-induced DNA damage can occasionally cause secondary acute myeloid leukemia involving MLL gene rearrangements at chromosome 11q23.

Indications

Symptomatic stage III and IV follicular lymphoma in previously untreated patients (in combination with cyclophosphamide, doxorubicin, prednisolone and interferon-alfa)Pediatric leukemiaSmall cell carcinomas of the lungTesticular tumors (in combination with bleomycin and cisplatin)Hodgkin diseaseLarge cell lymphomasNon-Hodgkin lymphomasAcute nonlymphocytic leukemiaKaposi sarcoma associated with AIDSTesticular tumoursLung cancerHodgkin’s lymphomaOther lymphomasCarcinoma bladderStomach carcinomaFirst-line treatment for Familial Hemophagocytic Lymphohistiocytosis (FHL)Component of HLH-94 and HLH-2004 treatment protocols for FHLImproved survival in secondary HLH when combined with glucocorticoidsSuggested addition for insufficient response in mild/moderate EBV-HLHComponent of severe EBV-HLH treatment (with dexamethasone and rituximab)Moderately dosed for malignancy-associated HLH to target cytokine storm and T-cell proliferationSecond- and third-line therapy for HLH-like complication of CAR T-cell therapy

Dosing

Adult: Etoposide may be given orally or by slow intravenous infusion; the oral dose being double the intravenous dose. Etoposide is usually given daily for 3–5 days and courses should not be repeated more frequently than at intervals of 21 days.
Renal adjustment: Consider dose reduction—consult local treatment protocol for details.
Hepatic adjustment: Manufacturer advises caution (increased risk of accumulation).

Pharmacokinetics

Half-life

6 to 8 h (terminal t1/2 in patients with normal renal function)

Bioavailability

Approximately 50% (oral)

Protein binding

Concentrations in the CSF average 1% to 10% of those in plasma. Toxicity increases in patients with decreased serum albumin, an effect related to decreased protein binding of the drug.

Excretion

Approximately 40% of an administered dose is excreted intact in the urine.

Contraindications

Pregnancy
Breastfeeding
In fertile individuals without effective contraception

Side effects

Common

NauseaVomitingFever (with intravenous use)Drowsiness (with oral use)Leukopenia (dose-limiting toxicity, nadir at 10–14 days, recovery by 3 weeks)StomatitisDiarrheaAlopecia (common but reversible)AlopeciaLeucopeniaG.i.t. disturbances

Serious

Angioedema (with intravenous use)
Extravasation necrosis (with intravenous use)
Infertility (with intravenous use)
Tumour lysis syndrome (with intravenous use)
Thrombocytopenia (less often and usually not severe)
Hepatic toxicity (particularly evident after high-dose treatment)
Hypotension and bronchospasm (from rapid intravenous administration due to additives)
Acute nonlymphocytic leukemia (unusual form with a translocation in chromosome 11q23, short time interval to onset, higher risk with cumulative doses >2000 mg/m2)