Etoposide (VP-16, VePesid, Toposar): Nadir, Side Effects and What to Expect

By the Oncol.net editorial team · Last updated November 1, 2026

Etoposide is a chemotherapy drug used mainly for small cell lung cancer and testicular cancer. The label says infection-fighting white cells reach their lowest point 7 to 14 days after the drug and platelets 9 to 16 days after, with bone marrow recovery usually complete by day 20. A temperature of 100.4°F (38°C) or higher during this time needs a call to your care team right away.

What etoposide is and how it works

Etoposide is a chemotherapy drug, also called VP-16. It belongs to a group called topoisomerase inhibitors. Topoisomerase II is an enzyme that cells use to untangle their DNA before they divide. Etoposide interferes with this step. The DNA strands break, the cell stops in its growth cycle, and it dies.

This hits fast-dividing cells hardest. Cancer cells are one target. Bone marrow, hair roots and the lining of the mouth and gut also divide quickly, which explains most of the side effects.

You may hear several names. Most etoposide in the US is generic. Toposar and VePesid are older brand names. Etopophos is etoposide phosphate, which the body converts to etoposide. Avopef is a newer branded etoposide injection that contains alcohol. They all deliver the same active drug, but they are not given in exactly the same way, so your team will choose the product and the dose.

What etoposide treats

Etoposide has two main FDA-approved uses. Both are given as part of a combination.

Small cell lung cancer: as a first treatment. Usually it is paired with cisplatin or carboplatin. For extensive-stage disease, chemotherapy is usually given with immunotherapy.
Testicular cancer: the label covers tumors that did not respond to earlier treatment. In practice it also appears in first-line testicular cancer regimens such as BEP (bleomycin, etoposide, cisplatin), EP (etoposide, cisplatin) and VIP (etoposide, ifosfamide, cisplatin). High-dose carboplatin and etoposide is another option.

MedlinePlus notes that it is also sometimes used for certain ovarian cancers. If you are getting etoposide for another cancer, ask your oncologist why it was chosen. Doctors can use approved drugs outside the label when evidence supports it, and some uses are being studied in clinical trials.

How etoposide is given

Etoposide injection goes into a vein as a slow drip, usually over 30 to 60 minutes. It should not be pushed in quickly, because a fast infusion can drop your blood pressure. Etopophos can be given over 5 minutes to 3.5 hours, but it is not given as a rapid push either.

Capsules are also available for small cell lung cancer. The label sets the capsule dose at twice the IV dose, rounded to the nearest 50 mg, because only about half is absorbed. Capsules are stored in the refrigerator and must not be frozen. MedlinePlus describes them as taken once a day for 4 or 5 days in a row.

These are typical label schedules, shown so you know what to expect. Your own dose is worked out from your height and weight (mg/m² means milligrams per square meter of body surface) and your kidney function.

Use	What you may see	Cycle length
Testicular cancer	50 to 100 mg/m² a day on days 1 to 5, or 100 mg/m² on days 1, 3 and 5	Repeats every 3 to 4 weeks after recovery
Small cell lung cancer (IV)	35 mg/m² a day for 4 days, or 50 mg/m² a day for 5 days	Repeats every 3 to 4 weeks after recovery
Small cell lung cancer (capsules)	Twice the IV dose, rounded to the nearest 50 mg	Repeats every 3 to 4 weeks after recovery

For small cell lung cancer, the American Cancer Society says first treatment usually runs 4 to 6 cycles. Kidney function matters: the label lowers the dose to 75% when creatinine clearance (a measure of kidney filtering) is 15 to 50 mL/min, and a further cut is considered below 15.

Nadir: when blood counts are lowest and when they recover

The nadir is the lowest point your blood counts reach after chemotherapy. Etoposide's effect on the bone marrow is the main limit on its dose, and it follows a fairly predictable pattern. The label states these timings:

Blood count	Lowest point	Recovery
Granulocytes (mostly neutrophils, the white cells that fight infection)	7 to 14 days after the drug	Usually complete by day 20
Platelets (the cells that help blood clot)	9 to 16 days after the drug	Usually complete by day 20

The label adds that no cumulative toxicity has been reported. In other words, this effect is not described as building up from one cycle to the next. That is the label's statement about etoposide. Other drugs in your regimen, and earlier treatment or radiation, can still change your counts.

One practical point: the label says "after drug administration" but does not say which day of a 3- or 5-day course to count from. Ask your team which dates they expect your counts to be lowest. The CDC advises every chemotherapy patient to ask this.

How common and how severe are low counts?

People often search for the rate of grade 4 neutropenia, the most severe drop. The current US labels we read do not give that figure. The injection label reports white cell and platelet results in these ranges:

Finding	Share of patients
White cells below 4,000/mm³	60% to 91%
White cells below 1,000/mm³	3% to 17%
Platelets below 100,000/mm³	22% to 41%
Platelets below 50,000/mm³	1% to 20%
Anemia (low red cells)	0% to 33%

The ranges are wide because the studies differ. Combinations can be different again, so your oncologist's estimate for your regimen is more useful than these numbers. Etopophos studies give another view: after doses of 90 to 110 mg/m², granulocytes fell by an average of 81% from the starting level, platelets by 44% and hemoglobin by 21%.

Treatment is held if platelets fall below 50,000/mm³ or the absolute neutrophil count falls below 500/mm³, until counts recover enough. Your blood is checked before each cycle. Read more about neutropenia and understanding blood counts. Some patients are given a growth factor such as pegfilgrastim or filgrastim.

Call your care team right away for a temperature of 100.4°F (38°C) or higher. The CDC calls fever during chemotherapy a medical emergency. Fever may be the only sign of infection. Use the number your team gave you if it is different. Check with them before taking medicine that lowers fever, because it can hide an infection.

Side effects and when they happen

Side effect	Timing and detail
Low blood pressure	During the infusion, in 1% to 2% of patients. It usually settles when the infusion is stopped.
Allergic-type reaction	During or soon after the infusion, in 0.7% to 2%. See the warning box below.
Nausea and vomiting	In 31% to 43%. Usually mild to moderate and managed with anti-nausea medicine.
Hair loss	In up to 66%, sometimes total. It reverses after treatment. NCI says hair often regrows 2 to 3 months after chemotherapy ends. See hair regrowth after chemo.
Low white cells and platelets	Lowest at about 7 to 16 days, recovered by about day 20.
Anemia and fatigue	Tiredness, pale skin and dizziness can build during treatment.
Mouth and throat sores, diarrhea, constipation	Listed as common for capsules by MedlinePlus. Tell your team if they are severe or do not go away.
Numbness or tingling in hands and feet	Listed by the American Cancer Society as a risk with etoposide. It is also common with cisplatin. It usually improves after treatment, but can last.
Skin damage at the IV site	If the drug leaks out of the vein, swelling, pain, cellulitis and skin damage can follow. Tell the nurse at once about pain or swelling at the site.

Rarely reported problems include severe skin reactions, lung inflammation, seizures, liver injury and temporary vision loss.

Serious warnings and when to call

Severe bone marrow suppression. The label warns of severe drops in blood counts, with infection or bleeding. Fatal cases have occurred, including opportunistic infections such as Pneumocystis pneumonia, a lung infection that takes hold when immunity is low.

Allergic-type reactions. These can include chills, fever, a fast heartbeat, wheezing, trouble breathing and low blood pressure. The infusion is stopped right away. A severe reaction means etoposide products should not be used again.

Second cancers. Acute leukemia has been reported rarely after etoposide. The American Cancer Society says a second cancer such as leukemia occurs in under 1% of patients treated with chemotherapy for testicular cancer. Your oncologist can put this small risk in context against the benefit of treatment.

Low albumin. Etoposide binds to albumin, a blood protein. People with low albumin may have more side effects, so tell your team about recent weight loss or poor eating.

Call your care team now if you have: a temperature of 100.4°F (38°C) or higher; shaking chills, sore throat or cough; bleeding that will not stop, black or bloody stools, or vomit that looks like coffee grounds; unusual bruising; rash or hives; or vomiting that keeps you from drinking. Call 911 for trouble breathing, swelling of the face or throat, fainting or a seizure. Tell emergency staff you are on chemotherapy. See when to call your doctor.

Interactions and precautions

Give your team a full list of your medicines, including over-the-counter drugs and supplements.

Warfarin: etoposide can raise your INR, the clotting test used for warfarin. Expect more frequent checks.
Seizure medicines: phenytoin, phenobarbital, carbamazepine and valproic acid may clear etoposide faster, which could lower how much drug you get.
Cisplatin: may raise etoposide levels. These two are often given together, and your team plans for this.
Cyclosporine at high levels: raised etoposide exposure by 80% when given with oral etoposide.
Aspirin: displaced etoposide from blood proteins in lab tests. Ask before taking it, and remember it also affects bleeding.
Live vaccines: avoid during treatment. Ask your team about timing for any vaccine.
Alcohol in the infusion: some products contain alcohol. Tell your team if you need to avoid it. Generic injection also contains benzyl alcohol.

Pregnancy, breastfeeding and fertility

Etoposide can harm a developing baby. The current Etopophos label gives this guidance:

Women who could become pregnant: use effective birth control during treatment and for 6 months after the last dose.
Men with partners who could become pregnant: use condoms or other effective birth control during treatment and for 4 months after the last dose.
Breastfeeding: do not breastfeed during treatment.

Fertility can be affected. In women, periods may stop, menopause can come early, and recovery of periods and ovulation depends on age at treatment. In men, sperm counts can fall or sperm can disappear, and fertility loss can be permanent. Sperm counts have returned to normal in some men, sometimes several years later. If you may want children, talk with your team before your first dose. Preserving sperm or eggs needs to be planned early.

Frequently asked questions

When is the etoposide nadir?

The label says granulocytes, the infection-fighting white cells, are lowest 7 to 14 days after the drug, and platelets are lowest 9 to 16 days after. Your team can tell you which dates to watch, because the label does not say which day of a multi-day course to count from.

When do blood counts recover after etoposide?

Bone marrow recovery is usually complete by day 20. This is why cycles usually repeat every 3 to 4 weeks, and only after you have recovered from side effects. If counts are still low, your team may delay the next cycle or change the dose.

What is the rate of grade 4 neutropenia with etoposide?

The current US labels we read do not give a grade 4 neutropenia percentage. The injection label reports white cells below 1,000/mm3 in 3% to 17% of patients and below 4,000/mm3 in 60% to 91%. Rates in combination regimens can differ, so ask your oncologist about your regimen.

Does the effect on blood counts get worse with each cycle?

The label says no cumulative toxicity has been reported, so this effect is not described as building up over cycles. Other drugs in your regimen and earlier treatment can still lower your counts, so blood tests are repeated before each cycle.

Will I lose my hair on etoposide?

Often, yes. The label reports reversible hair loss in up to 66% of patients, and it sometimes becomes total. The National Cancer Institute says hair often regrows 2 to 3 months after chemotherapy ends. New hair may be finer or a different texture at first.

What is the difference between etoposide and Etopophos?

Etopophos is etoposide phosphate, a form the body fully converts to etoposide. It has the same approved uses and the same warnings about blood counts. The main practical difference is that it can be infused over 5 minutes to 3.5 hours, while standard etoposide injection is usually given over 30 to 60 minutes.

Can etoposide cause leukemia?

It can, but this is rare. The label reports acute leukemia in rare instances, and the Etopophos label links it with long-term use. Ask your oncologist how this small risk compares with the benefit of treatment for you.

Sources

This page is general information, not medical advice. Your care team knows your situation and should guide your decisions.