Cisplatin and Etoposide: What to Expect

This page is for people about to start cisplatin and etoposide (EP), often used for small cell lung cancer. It covers how the drugs work, what a cycle and a treatment day look like, the main risks, and when to call for help.

Cisplatin is a platinum compound. It sticks to DNA and forms cross-links that a dividing cell cannot repair. Etoposide blocks topoisomerase II, an enzyme that untangles DNA strands while a cell copies them. Because the two drugs damage cells by separate routes, they are paired rather than used alone. On charts and consent forms the pair is written EP or PE.

One detail surprises people. The FDA label for etoposide injection does list small cell lung cancer as a first-line use, in combination with other approved drugs. Cisplatin's label does not. Cisplatin is approved for advanced testicular cancer, advanced ovarian cancer, and advanced bladder cancer. Its use in lung cancer rests on decades of trial data and guideline agreement, not on the package insert. This is routine in cancer care, but it is useful to know if an insurer questions the claim.

Treatment is given in cycles. Ask your team how long each cycle lasts and which days each drug is given.

Doses are written per square meter of body surface area, shortened to mg/m2. That figure comes from your height and weight, so no two people get the same milligram number. The etoposide label sets out a range for small cell lung cancer, given daily for four or five days in a row. Your own schedule may differ, so ask the infusion pharmacist for the exact numbers on your order.

Cisplatin dosing on the label is listed by approved use, and the pattern differs: daily for five days in testicular cancer, and a single larger dose every 3 to 4 weeks in ovarian and bladder cancer. The label gives no lung cancer schedule, so your team sets that from trial and guideline experience.

Etoposide has to be diluted within a narrow range of strengths. Any more concentrated and the drug can fall out of solution. It runs over 30 to 60 minutes and is never pushed quickly, because fast injection has caused a brief drop in blood pressure in 1% to 2% of patients.

Cisplatin cannot be given dry. The label requires fluid before the drug and says urine output must be kept up for a full 24 hours afterward. Expect saline first, saline again at the end, and often magnesium and potassium added to the bag.

The cisplatin label calls it highly emetogenic (likely to cause vomiting). That means vomiting is expected without prevention rather than merely possible. The National Cancer Institute's summary for clinicians describes a four-drug block: an NK-1 receptor blocker such as aprepitant or its intravenous form fosaprepitant, a 5-HT3 blocker such as palonosetron or ondansetron, the steroid dexamethasone, and olanzapine. In the trial NCI cites, olanzapine was 10 mg by mouth on days 1 through 4. Add the fluids and the pre-medicines and a first day can be long. Ask how long to plan for, and bring food and a phone charger.

Olanzapine is one you would swallow at home in the days after the drip, so the timing matters. Ask your team which days and what amount to take. It works best used as prevention, so it is often taken even when you are not being sick.

Cisplatin carries one boxed warning covering kidney injury, peripheral neuropathy, nausea and vomiting, and myelosuppression.

Kidney damage is dose-related and builds up. The label notes it typically starts during the second week after a dose, which is why kidney blood tests (creatinine, BUN, creatinine clearance) and electrolytes (blood salts) including magnesium are checked before the first cycle and again later. Magnesium wasting is common enough that the label names supplements directly. Kidney problems during cancer treatment covers what those numbers mean.

Peripheral neuropathy means numbness, tingling, or burning that starts in the fingers and toes. The label says to consider stopping cisplatin permanently for grade 3 or grade 4 neuropathy, meaning symptoms that limit self-care.

Myelosuppression, a drop in blood cells made by the marrow, occurs in 25% to 30% of people on cisplatin. Etoposide adds to it. Low white blood cells during chemotherapy explains the timing of the dip. These figures come from the FDA’s “Cisplatin Injection Prescribing Information.”

Hearing loss is a separate warning, not part of the boxed one. The label describes ringing in the ears, loss of high-pitched hearing (4,000 to 8,000 Hz), and trouble hearing normal conversation. It can happen during or after treatment. The damage is cumulative and may be severe. In children the estimated rate is 40% to 60%, and risk is highest under age 5. See hearing loss and tinnitus from cisplatin.

For limited-stage small cell lung cancer, EP is often paired with chest radiation given concurrently. NCI's clinician summary reports Intergroup 0096, which compared twice-daily radiation to 45 Gy over three weeks against once-daily 45 Gy over five weeks, both with cisplatin and etoposide. Five-year survival was 26% with twice-daily and 16% with once-daily. Esophagitis, painful swelling of the swallowing tube, was worse on the twice-daily arm. NCI also notes that finishing radiation in under 30 days was linked to better five-year survival, with a relative risk of 0.62.

Age changes the math. In the EST-3588 trial, treatment-related death was 1% in people under 70 and 10% in those 70 or older.

A Hellenic Oncology Group trial compared cisplatin plus etoposide with carboplatin plus etoposide. Median survival was 11.8 months with cisplatin and 12.5 months with carboplatin. The difference was not significant, and NCI notes the study was too small to prove the two are equal. NCI notes that carboplatin is dosed by kidney function and causes fewer side effects outside the blood counts than cisplatin, which needs extra fluids. Lung cancer treatment by stage shows where each fits.

• Call your cancer team without delay if your temperature is 100.4°F (38°C) or higher. Etoposide and cisplatin lower the white cells that fight infection, and CDC treats a fever during chemotherapy as a medical emergency, so this is a call to make at once, at any hour, and not a message left for the morning. If the team cannot be reached quickly, go to an emergency department and say you are on chemotherapy.
• Seek emergency care right away if you suddenly cannot pass any urine. Go to the nearest emergency department or call 911.
• Call your care team right away if you pass much less urine than usual, or you cannot keep fluids down. Both put the kidneys at risk, and the label says urine output must be kept up after cisplatin.
• Call 911 or go to the nearest emergency department if you have black, tarry stools, vomit blood or material that looks like coffee grounds, or have heavy bleeding. Do not drive yourself if you feel very unwell.
• Call your care team right away if new ringing in the ears, muffled hearing, or dizziness appears. Do the same for new pain, burning, tingling or numbness in the hands or feet. MedlinePlus says to call your doctor immediately for these. Do not change or stop doses yourself.

• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=508496cb-3441-46b3-a4fe-e0d440e6adc6
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe870629-104d-4d67-a7c6-f53bc588121e
• https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
• https://www.cancer.gov/about-cancer/treatment/side-effects/nausea/nausea-hp-pdq
• https://www.cancer.gov/about-cancer/treatment/side-effects/infection
• https://medlineplus.gov/ency/patientinstructions/000913.htm
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html