Etopofos
Etoposide Phosphate – Intravenous Chemotherapy for Cancer Treatment
Quick Facts About Etopofos
Key Takeaways About Etopofos
- Hospital-only chemotherapy: Etopofos is administered exclusively by healthcare professionals as an intravenous infusion in a hospital or specialised cancer centre
- Bone marrow suppression is the main risk: Regular blood tests are essential before and during each treatment cycle to monitor blood cell counts
- Effective against multiple cancers: Used for testicular cancer, small cell lung cancer, acute myeloid leukaemia, Hodgkin's and non-Hodgkin's lymphoma, and gynaecological cancers
- Must never be given rapidly: The infusion must be administered slowly over 30–60 minutes to avoid dangerous drops in blood pressure
- Contraception is essential: Both men and women must use effective contraception during treatment and for at least 6 months after the final dose
What Is Etopofos and What Is It Used For?
Etopofos is a chemotherapy medication containing etoposide phosphate, a water-soluble prodrug that is converted to etoposide in the body. It belongs to the class of cytostatic drugs known as topoisomerase II inhibitors and is used to treat a range of cancers in both adults and children.
Etopofos contains the active substance etoposide phosphate. Each vial contains etoposide phosphate equivalent to 100 mg of etoposide. Once administered intravenously, the body's natural enzymes (alkaline phosphatases) rapidly convert etoposide phosphate into its active form, etoposide. The key advantage of this prodrug formulation is its superior water solubility, which allows for more stable and convenient preparation compared to conventional etoposide formulations that require organic solvents.
Etoposide works by inhibiting topoisomerase II, an essential enzyme that helps manage the complex process of DNA replication during cell division. DNA must be unwound and separated for cells to divide, and topoisomerase II facilitates this by creating temporary breaks in the DNA double strand. Etoposide stabilises the complex between topoisomerase II and DNA, preventing the enzyme from re-joining the broken DNA strands. This leads to irreversible DNA double-strand breaks that trigger programmed cell death (apoptosis). Because cancer cells divide more rapidly than most normal cells, they are particularly vulnerable to this mechanism of action.
Etoposide is cell-cycle specific, exerting its greatest effect during the late S phase and the G2 phase of the cell cycle – the periods when cells are actively preparing for and entering division. This cell-cycle specificity is one reason why etoposide is typically administered over multiple consecutive days in each treatment cycle, allowing it to catch cancer cells as they progress through vulnerable phases of division.
Approved Indications in Adults
Etopofos is used to treat the following types of cancer in adults:
- Testicular cancer – typically as part of the BEP regimen (bleomycin, etoposide, cisplatin), which is the standard first-line chemotherapy for disseminated testicular germ cell tumours
- Small cell lung cancer (SCLC) – usually combined with cisplatin or carboplatin as the cornerstone of first-line treatment, as recommended by the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN)
- Acute myeloid leukaemia (AML) – used in various induction and consolidation chemotherapy regimens
- Hodgkin's lymphoma – typically as part of multi-drug regimens for relapsed or refractory disease
- Non-Hodgkin's lymphoma – used in combination chemotherapy for aggressive lymphomas
- Gestational trophoblastic neoplasia – in combination regimens for high-risk or resistant disease
- Ovarian cancer – used in certain combination chemotherapy protocols
Approved Indications in Children
In paediatric patients, Etopofos is used for:
- Acute myeloid leukaemia (AML) – as part of intensive combination chemotherapy protocols
- Hodgkin's and non-Hodgkin's lymphoma – in age-appropriate multi-agent chemotherapy regimens
Etoposide was originally derived from podophyllotoxin, a natural compound found in the American mayapple plant (Podophyllum peltatum). It was first approved for medical use in 1983 and has since become one of the most widely used chemotherapy agents worldwide. It is included on the World Health Organization’s List of Essential Medicines, underscoring its fundamental importance in cancer treatment globally.
What Should You Know Before Receiving Etopofos?
Before starting Etopofos treatment, your medical team will assess your overall health, blood counts, liver and kidney function, and current medications. Certain conditions and medications are incompatible with etoposide treatment, so a thorough medical review is essential.
Contraindications
You should not receive Etopofos if any of the following apply to you:
- Allergy to etoposide or etoposide phosphate – or to any of the other ingredients in the formulation (sodium citrate, Dextran 40). Symptoms of a previous allergic reaction may have included skin rash, swelling, or breathing difficulties
- Recent vaccination with a live vaccine – including yellow fever vaccine. Live vaccines can cause serious or life-threatening infections in patients whose immune systems are suppressed by chemotherapy. You should not receive live vaccines during or shortly before starting etoposide treatment
- Breastfeeding – etoposide may pass into breast milk and could harm the nursing infant. Breastfeeding must be stopped before starting treatment and must not be resumed during treatment
- Severe bone marrow suppression – patients with very low blood cell counts are at increased risk of life-threatening infection or bleeding
Warnings and Precautions
Talk to your doctor or medical team before receiving Etopofos if you have or have had any of the following:
- Any active infections – infections should be treated before starting chemotherapy, as etoposide suppresses the immune system and can make existing infections much worse
- Recent radiotherapy or chemotherapy – prior treatments may have already reduced your bone marrow reserve, increasing the risk of severe myelosuppression with etoposide
- Low serum albumin levels – etoposide is highly protein-bound (approximately 97%), and low albumin levels increase the amount of free (active) drug in the blood, potentially intensifying side effects
- Liver problems – etoposide is primarily metabolised by the liver, and impaired liver function can lead to higher drug exposure and increased toxicity
- Kidney problems – impaired kidney function slows the elimination of etoposide and may require dose adjustments
Effective cancer treatment can rapidly destroy large numbers of cancer cells, releasing harmful substances into the bloodstream. This condition, known as tumour lysis syndrome (TLS), can cause serious damage to the kidneys, heart, and liver, and can be life-threatening if not treated promptly. Your medical team will monitor you with regular blood tests and may prescribe preventive measures such as adequate hydration and uric acid–lowering medications (e.g. allopurinol or rasburicase) before starting treatment.
Your medical team will perform regular blood tests throughout your treatment. Complete blood counts will be checked before each treatment cycle and between cycles to ensure your bone marrow is recovering adequately. If your blood counts are too low, your next treatment cycle may be delayed until they recover to safe levels. Additional blood tests may be performed to monitor liver and kidney function, particularly if you have pre-existing impairment of these organs.
Pregnancy, Breastfeeding, and Fertility
Etopofos can cause serious harm to an unborn child. It must not be used during pregnancy unless your doctor considers the potential benefit to outweigh the risks, and only after a thorough discussion of the dangers. If you are of childbearing potential, a pregnancy test should be performed before starting treatment.
Breastfeeding must be discontinued before starting Etopofos, as etoposide or its metabolites may pass into breast milk and could harm the nursing infant.
Both male and female patients who could potentially become parents must use effective contraception (such as a barrier method or condom) during treatment and for at least 6 months after the last dose of Etopofos. Etoposide is known to be genotoxic and mutagenic, meaning it can damage genetic material, which poses risks to future offspring.
Male patients are specifically advised not to father a child during treatment and for up to 6 months afterwards. Because etoposide can cause infertility, men are encouraged to seek information about sperm banking before starting treatment if they wish to have children in the future.
Both male and female patients who are considering having children after treatment should discuss fertility preservation options with their medical team before starting chemotherapy.
Driving and Operating Machinery
The effects of Etopofos on the ability to drive and use machines have not been formally studied. However, because etoposide can cause tiredness, nausea, dizziness, and drowsiness, you should not drive or operate machinery if you experience any of these symptoms. You are personally responsible for assessing your fitness to drive and should discuss this with your doctor if you are uncertain.
Sodium Content
Etopofos contains less than 1 mmol of sodium (23 mg) per vial, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
How Does Etopofos Interact with Other Drugs?
Etopofos can interact with several medications, including immunosuppressants, anticonvulsants, anticoagulants, anti-inflammatory drugs, and other chemotherapy agents. Always inform your medical team about all medications you are taking, including prescription drugs, over-the-counter products, and herbal supplements.
Etoposide (the active metabolite of etoposide phosphate) is approximately 97% bound to plasma proteins and is metabolised primarily by the liver enzyme CYP3A4. Drugs that affect protein binding, liver metabolism, or kidney function can alter etoposide levels in the body, potentially increasing toxicity or reducing effectiveness. The following table summarises the most clinically significant interactions.
Major Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Cyclosporine | Immunosuppressant | Significantly increases etoposide blood levels by reducing clearance, leading to increased toxicity risk | Dose adjustment of etoposide required; close monitoring of blood counts essential |
| Cisplatin | Chemotherapy (platinum agent) | May reduce etoposide clearance when given concurrently; additive myelosuppression and nephrotoxicity | Monitor kidney function and blood counts closely; standard combination in many protocols |
| Live vaccines (e.g. yellow fever, MMR, varicella) | Vaccines | Risk of severe, potentially fatal generalised vaccine disease due to immunosuppression | Absolutely contraindicated; use inactivated vaccines where available |
| Warfarin | Anticoagulant | Etoposide may increase the anticoagulant effect, raising the risk of bleeding | Monitor INR frequently; dose adjustment of warfarin may be needed |
| Anthracyclines (e.g. doxorubicin, epirubicin) | Chemotherapy | Additive myelosuppression and potential cardiotoxicity | Monitor cardiac function and blood counts; adjust timing and doses as per protocol |
Moderate Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Phenytoin | Anticonvulsant | Phenytoin induces CYP3A4, potentially reducing etoposide efficacy; etoposide may reduce phenytoin absorption | Monitor phenytoin levels and seizure control; dose adjustments may be needed for both drugs |
| Phenylbutazone | NSAID | Displaces etoposide from protein binding sites, increasing free drug levels and toxicity risk | Avoid concurrent use where possible; monitor closely if combination is unavoidable |
| Sodium salicylate / Acetylsalicylic acid | Analgesic / Anti-inflammatory | May displace etoposide from protein binding, increasing free drug concentration | Use alternative analgesics (e.g. paracetamol) where possible; avoid high-dose aspirin |
| Other CYP3A4 inhibitors (e.g. ketoconazole, itraconazole) | Antifungals | May increase etoposide blood levels by inhibiting hepatic metabolism | Monitor for increased toxicity; consider dose reduction if combined |
During and after Etopofos treatment, your immune system will be weakened. All live vaccines are strictly contraindicated. Inactivated vaccines (such as influenza injection and COVID-19 mRNA vaccines) may be given, but the immune response may be reduced. Discuss your vaccination schedule with your oncologist.
What Is the Correct Dosage of Etopofos?
Etopofos is given as a slow intravenous infusion over 30 to 60 minutes. Dosing is individualised based on body surface area, the type of cancer being treated, and the patient's kidney function. It must never be given as a rapid intravenous injection.
The dose of Etopofos is calculated based on body surface area (BSA), expressed in mg/m². Your medical team will determine the exact dose based on your height, weight, type of cancer, overall health status, and any previous treatments. Doses are expressed as etoposide equivalents.
Adults
Standard Adult Dosing Regimens
Regimen 1: 50 to 100 mg/m²/day intravenously on days 1 through 5 of each cycle
Regimen 2: 100 to 120 mg/m² intravenously on days 1, 3, and 5 of each cycle
Treatment cycles are repeated every 3 to 4 weeks (minimum 21 days from the start of the previous cycle), provided blood counts have recovered to acceptable levels. The exact regimen depends on the type of cancer and the combination of other chemotherapy drugs being used.
Children
Paediatric Dosing
For children with acute myeloid leukaemia or lymphoma: 75 to 150 mg/m²/day intravenously for 2 to 5 consecutive days, in combination with other anti-cancer agents. The specific regimen is determined by local treatment guidelines and the child's oncologist.
Elderly Patients
No specific dose adjustments are required for elderly patients (over 65 years) based on age alone. However, dose adjustments may be necessary based on kidney function, which tends to decline with age. Your doctor will assess your kidney function before and during treatment.
Dose Adjustments for Kidney Impairment
| Creatinine Clearance | Recommended Dose | Notes |
|---|---|---|
| >50 ml/min | 100% of standard dose | No adjustment needed |
| 15–50 ml/min | 75% of standard dose | Close monitoring of blood counts required |
| <15 ml/min (dialysis) | Further dose reduction | Specialist assessment required; consider alternative treatments |
Subsequent doses should be adjusted based on individual patient tolerance and clinical response. For patients with a creatinine clearance below 15 ml/min who are receiving dialysis, additional dose reductions should be considered.
Overdose
Because Etopofos is administered by healthcare professionals in a controlled hospital setting, overdose is unlikely. However, if an overdose were to occur, the primary concern would be severe bone marrow suppression, leading to dangerously low levels of white blood cells (neutropenia), red blood cells (anaemia), and platelets (thrombocytopenia). There is no specific antidote for etoposide overdose; treatment is supportive, including blood transfusions, growth factor support (e.g. G-CSF), and management of any infections that may develop.
Etopofos must NEVER be given as a rapid intravenous injection. It must always be administered as a slow infusion over at least 30 to 60 minutes. Rapid injection has been associated with severe hypotension (dangerously low blood pressure), which can be life-threatening. Healthcare professionals must also take precautions to avoid extravasation (leakage of the drug outside the vein), which can cause local tissue damage.
What Are the Side Effects of Etopofos?
Like all chemotherapy medications, Etopofos can cause side effects. The most significant is bone marrow suppression, which affects blood cell production. Other common effects include hair loss, nausea, vomiting, and fatigue. Tell your medical team immediately if you develop any signs of infection, unusual bleeding, or allergic reactions.
Not everyone who receives Etopofos will experience all of the side effects listed below. The severity and frequency of side effects depend on the dose, the duration of treatment, and whether Etopofos is used alone or in combination with other chemotherapy agents. Your medical team will monitor you closely and can provide treatments to help manage many of these effects.
Swollen tongue or throat, difficulty breathing, rapid heartbeat, widespread skin redness or rash. These may be signs of a severe allergic reaction (anaphylaxis), which requires emergency treatment.
Very Common Side Effects
- Bone marrow suppression (myelosuppression) – low white blood cells (leucopenia/neutropenia), low red blood cells (anaemia), and low platelets (thrombocytopenia). This is the dose-limiting toxicity and the reason for regular blood tests between cycles
- Temporary hair loss (alopecia) – usually reversible after treatment ends
- Nausea and vomiting – anti-emetic medications will usually be prescribed to help prevent or reduce these
- Abdominal pain
- Loss of appetite (anorexia)
- Constipation
- Fatigue and general malaise (asthenia)
- Skin pigmentation changes
- Liver toxicity (hepatotoxicity) – elevated liver enzymes, jaundice (elevated bilirubin)
Common Side Effects
- Acute leukaemia – secondary leukaemia (treatment-related AML) has been reported following etoposide therapy
- Irregular heartbeat (arrhythmia) or heart attack (myocardial infarction)
- Dizziness
- Diarrhoea
- Injection site reactions – redness, swelling, or pain at the infusion site
- Severe allergic reactions
- High blood pressure (hypertension) or low blood pressure (hypotension)
- Mouth sores (mucositis) – sore lips, ulcers in the mouth or throat
- Skin problems – itching (pruritus) or rash
- Phlebitis – inflammation of a vein
- Infections – including opportunistic infections such as Pneumocystis jiroveci pneumonia
Uncommon Side Effects
- Tingling or numbness in hands and feet (peripheral neuropathy)
- Bleeding (haemorrhage)
Rare Side Effects
- Acid reflux
- Facial flushing
- Difficulty swallowing (dysphagia)
- Changes in taste (dysgeusia)
- Seizures (convulsions)
- Fever
- Drowsiness or excessive tiredness (somnolence)
- Breathing difficulties (bronchospasm, pulmonary toxicity)
- Temporary blindness – cortical blindness, usually reversible
- Severe skin reactions – Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are serious, potentially life-threatening conditions involving widespread skin blistering and peeling
- Radiation recall dermatitis – a sunburn-like reaction on skin previously treated with radiotherapy
Frequency Not Known
- Tumour lysis syndrome – potentially life-threatening metabolic complication from rapid cancer cell destruction
- Swelling of face and tongue (angioedema)
- Infertility
- Respiratory failure
- Acute kidney failure
Etoposide, like some other topoisomerase II inhibitors, has been associated with the development of secondary acute myeloid leukaemia (treatment-related AML), typically occurring months to years after treatment. This risk is related to cumulative dose and treatment duration. The risk-benefit ratio strongly favours treatment in the cancers for which etoposide is indicated, but your oncologist will consider this when planning your treatment.
How Should Etopofos Be Stored?
Etopofos must be stored in a refrigerator (2°C–8°C), protected from light, and kept out of reach of children. As a hospital medication, storage is managed by pharmacy staff in accordance with strict handling protocols for cytotoxic drugs.
Etopofos should be stored under the following conditions:
- Keep out of sight and reach of children
- Do not use after the expiry date printed on the carton and vial after “EXP”. The expiry date refers to the last day of the stated month
- Store in a refrigerator at 2°C to 8°C
- Keep the vial in the outer carton to protect from light
Once reconstituted (mixed with a suitable solution for infusion), Etopofos should be used as soon as possible. Your hospital pharmacy will follow local guidelines for the stability and handling of reconstituted solutions. Any unused solution should be disposed of in accordance with local regulations for cytotoxic waste – it must not be poured down drains or discarded as household waste.
Preparation Information (For Healthcare Professionals)
Etopofos is reconstituted under aseptic conditions by adding 5 ml or 10 ml of water for injection, 5% glucose solution, or 0.9% sodium chloride solution to each vial, producing concentrations of 20 mg/ml or 10 mg/ml etoposide equivalent respectively. The reconstituted solution may be further diluted with 5% glucose or 0.9% sodium chloride to concentrations as low as 0.1 mg/ml. Only clear solutions should be used; cloudy or discoloured solutions must be discarded. Etopofos must not be mixed with any other medication.
What Does Etopofos Contain?
Each Etopofos vial contains etoposide phosphate equivalent to 100 mg of etoposide as the active substance, along with sodium citrate and Dextran 40 as inactive ingredients. It is a white to off-white powder supplied in glass vials.
Active Substance
The active substance is etoposide phosphate. Each vial contains etoposide phosphate equivalent to 100 mg of etoposide. Etoposide phosphate is the water-soluble phosphate ester prodrug of etoposide, which is rapidly converted to etoposide by endogenous alkaline phosphatases after intravenous administration.
Other Ingredients (Excipients)
- Sodium citrate – used as a buffering agent to maintain the appropriate pH
- Dextran 40 – a polysaccharide used as a stabilising agent in the powder formulation
Appearance and Pack Sizes
Etopofos is a white to off-white powder supplied in a glass vial with a butyl rubber stopper and aluminium cap seal. It is available in packs of 1, 5, or 10 vials. Not all pack sizes may be marketed in all countries.
Manufacturer
Etopofos is manufactured by Latina Pharma S.p.A. (Sermoneta, Italy) and Prestige Promotion Verkaufsförderung & Werbeservice GmbH (Alzenau, Germany) for the marketing authorisation holder CHEPLAPHARM Arzneimittel GmbH (Greifswald, Germany).
Frequently Asked Questions About Etopofos
Etopofos contains etoposide phosphate, which is a water-soluble prodrug of etoposide. After intravenous administration, etoposide phosphate is rapidly and completely converted to etoposide in the body by alkaline phosphatase enzymes. The anti-cancer activity is identical. The main advantage of etoposide phosphate (Etopofos) is its superior water solubility, which means it can be reconstituted and diluted without organic solvents (such as polysorbate 80, polyethylene glycol, or ethanol) that are required for conventional etoposide formulations. This reduces the risk of precipitation, hypersensitivity reactions related to solvents, and allows faster preparation.
The duration of Etopofos treatment depends on the type of cancer, how well it responds to therapy, and which other drugs are used in combination. A typical treatment cycle involves infusions over 3 to 5 consecutive days, with cycles repeated every 3 to 4 weeks. The total number of cycles varies: for testicular cancer, 3 to 4 cycles of the BEP regimen is standard; for small cell lung cancer, 4 to 6 cycles of etoposide-platinum combination is typical. Your oncologist will determine the optimal treatment duration based on your individual response and tolerance.
Yes, hair loss caused by etoposide is typically temporary and reversible. Most patients begin to see hair regrowth within 2 to 3 months after completing chemotherapy. The new hair may initially have a slightly different texture or colour, but this usually normalises over time. Scalp cooling during infusion may help reduce the extent of hair loss in some patients, though its effectiveness varies. Discuss options for managing hair loss with your medical team.
Live vaccines (such as yellow fever, MMR, varicella, and oral polio) are strictly contraindicated during Etopofos treatment and for a period after treatment ends, as your suppressed immune system cannot safely handle live vaccine organisms. Inactivated vaccines (such as the influenza injection, COVID-19 mRNA vaccines, and pneumococcal vaccine) can generally be given, although the immune response may be weaker than normal. Your oncologist will advise you on the appropriate timing for any vaccinations based on your treatment schedule and immune recovery.
A fever during chemotherapy (especially a temperature of 38°C / 100.4°F or higher) must be taken seriously, as it may be a sign of febrile neutropenia – an infection in a patient with dangerously low white blood cell counts. This is a medical emergency that requires urgent evaluation and often intravenous antibiotics. Contact your oncology team or go to the emergency department immediately if you develop a fever during treatment. Do not take paracetamol or other fever-reducing medications to mask a temperature without first contacting your medical team.
Yes, Etopofos is approved for use in paediatric patients for the treatment of acute myeloid leukaemia (AML) and lymphomas (both Hodgkin's and non-Hodgkin's). The dosing range in children is 75 to 150 mg/m²/day for 2 to 5 days, in combination with other chemotherapy agents. The specific treatment regimen is determined by paediatric oncology protocols and local treatment guidelines. Children receiving etoposide require the same careful blood count monitoring as adult patients.
References
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Editorial Team
iMedic Medical Editorial Team – Specialists in oncology, haematology, and clinical pharmacology with extensive experience in cytotoxic drug therapy and cancer treatment protocols.
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