Etoposide

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 16.02.2021

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Synonym(s)

CAS number: 117091-64-2 (Phosphat); CAS number: 33419-42-0; ETO; VP16; VP-16

Definition
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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.

Pharmacodynamics (Effect)
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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.

Indication
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  • 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.

Dosage and method of use
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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

Undesirable effects
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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

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

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

Renal and urinary tract disorders

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

Contraindication
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Hypersensitivity to the active substance, podophyllotoxin and podophyllotoxin derivatives

Use of a yellow fever vaccine or other live vaccines

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

Authors

Last updated on: 16.02.2021