Etoposide

Etoposide is chemically speaking, a glycoside of podophyllotoxin (molecular formula: C29H32O13), which is extracted from the root of the evergreen American May Apple(Podophyllum peltatum). Etoposide is used chemically unchanged or in the form of its phosphoric acid ester (etoposide phosphate) as a cytostatic drug in chemotherapy. It inhibits the enzyme topoisomerase II.

Etoposide is used chemically unchanged or in the form of its phosphoric acid ester (etoposide phosphate) as a cytostatic drug in chemotherapy. It inhibits the enzyme topoisomerase II.

Topoisomerases of type I relax the DNA, transform a superhelical DNA into a relaxed DNA by reversibly cleaving a strand of duplex DNA. This creates the prerequisite for reading, i.e. transcription of the DNA. After successful DNA replication, the DNA gap is closed again. Type I topisomerase always reversibly cleaves only one strand of DNA. Topoisomerase inhibitors I allow DNA cleavage, stabilise the topoisomerase-DNA complex and prevent the enzyme from closing the cleavage site again. This leads to the breakage of the DNA strand and the cell is driven into apoptosis. Topoisomerase inhibitor I develops the strongest antineoplastic activity in the S phase.

The type II topoisomerases act ATP-dependent. They are able to separate both DNA strands. In the case of etoposide, a semi-synthetic glycosidic podophyllotoxin derivative, the glycoside binds with the DNA and the topoisomerase to form a stable complex that allows the cleavage of the DNA double strand but prevents the re-closure of the resulting DNA gap. The enzyme remains bound to the free end of the DNA. The transcription comes to a standstill. The cell gives the signal for its own cell death (apoptosis) because the arrest of DNA relaxation can no longer be released.

• Testicular cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the first-line treatment of recurrent or refractory testicular cancer in adults.
• Small cell lung cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of small cell lung cancer in adults.
• Hodgkin's lymphoma: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of Hodgkin's lymphoma in adult and pediatric patients.
• Non-Hodgkin's lymphoma: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of non-Hodgkin's lymphoma in adult and pediatric patients.
• Acute myeloid leukemia: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of acute myeloid leukemia in adult and pediatric patients.
• Gestational trophoblastic neoplasia: Etoposide is indicated for first-line and second-line treatment in combination with other approved chemotherapeutic agents for the treatment of gestational high-risk trophoblastic neoplasia in adults.
• Ovarian cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of non-epithelial ovarian cancer in adults. Etoposide is indicated for the treatment of platinum resistant/refractory epithelial ovarian cancer in adults.

The recommended dose of etoposide in adult patients is 50-100 mg/m2/day on day 1-5 or 100-120 mg/m2 on days 1, 3 and 5 every 3-4 weeks in combination with other drugs indicated for the disease to be treated.

Children and adolescents (Hodgkin's lymphoma; non-Hodgkin's lymphoma; acute myeloid leukaemia): Etoposide has been used in pediatric patients in the dose range 75-150 mg/m2/day for 2-5 days in combination with other antineoplastic drugs. The appropriate treatment regimen should be selected based on current standard local treatment protocols

Classification according to system organ class as well as designation of side effects according to MedDRA.

Frequencies are subdivided according to:

• very common: > 1 in 10, common: > 1 in 100, occasional: > 1 in 1000, rare: > 1 in 10 000, very rare: < 1 in 10 000.

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Infections and parasitic diseases

• Common: Infections

Benign, malignant and non-specific neoplasms (including cysts and polyps)

• Frequent: acute leukaemia

Blood and lymphatic system disorders

• Very common: Anaemia, leucopenia, myelosuppression, neutropenia, thrombocytopenia

Diseases of the immune system

• Frequent: anaphylactic reactions
• Not known: Angioedema, bronchospasm

Metabolic and nutritional disorders

• Not known: tumor lysis syndrome

Nervous system disorders

• Frequent: Dizziness
• Occasional: peripheral neuropathy
• Rare: transient cortical blindness, neurotoxicities (e.g., somnolence and fatigue), optic neuritis, seizures

Heart disease

• Common: myocardial infarction, arrhythmia

Vascular disorders

• Frequent: hypertension, transient systolic hypotension after rapid intravenous administration
• Occasionally: Bleeding

Respiratory, thoracic and mediastinal disorders

• Rare: interstitial pneumonitis, pulmonary fibrosis
• Not known: Bronchospasm

Gastrointestinal disorders:

• Very common: abdominal pain, anorexia, constipation, nausea and vomiting.
• Frequent: diarrhoea, mucositis (including stomatitis and oesophagitis)
• Rarely: taste disturbance, dysphagia

Liver and biliary disorders

• Very common: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, hepatotoxicity

Skin and subcutaneous tissue disorders

• Very common: diffuse effluvium and alopecia, hyperpigmentation
• Frequent: pruritus, exanthema, urticaria
• Rare: radiation recall dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN)

Renal and urinary tract disorders

• Not known: acute renal failure

Diseases of the genital organs and mammary gland

• Not known: Infertility

General diseases and complaints at the place of administration

• Very common: Asthenia, malaise
• Common: Local soft tissue toxicity, swelling, pain and necrosis, including skin necrosis, phlebitis have been reported with extravasation.
• Rare: Fever

Hypersensitivity to the active substance, podophyllotoxin and podophyllotoxin derivatives

Use of a yellow fever vaccine or other live vaccines

Eto-cell® (D), Eto-Gry® (D), Etomedac® (D), Etopophos® (D, A, CH), Lastet® (D), Neoposid® (D), Riboposid ^®(D), Vepesid® (D, A, CH, USA)