Cisplatin-Pemetrexed — The Non-Squamous Lung Standard
Your chart says Cisplatin-Pemetrexed — or sometimes Platinum-Pemetrexed. Both mean the same regimen: pemetrexed paired with a platinum drug, used for non-squamous lung cancer. The folic acid and vitamin B12 are part of the treatment itself, not extras.
- Two-drug combination — Pemetrexed, an antifolate, plus cisplatin or carboplatin — together the standard for non-squamous NSCLC.
- Non-squamous only — Not used for squamous cell carcinoma or small cell lung cancer. The histology determines whether this regimen applies.
- Vitamins are part of treatment — Folic acid and vitamin B12 reduce toxicity from pemetrexed. They are required before the first cycle begins.
- Given as day care — Each infusion cycle is outpatient. Sessions take several hours, but you go home the same day.
Medically reviewed by Dr. Owais Mohammed, Medical Oncologist · Last reviewed September 2026
Cisplatin-pemetrexed is a two-drug regimen for non-squamous non-small cell lung cancer — most often adenocarcinoma. Pemetrexed is an antifolate; cisplatin is the platinum drug. Folic acid tablets and a vitamin B12 injection are started before the first cycle. Both are a required part of the protocol, not optional supplements.
What happens across a treatment cycle?
Vitamin preparation before your first cycle
Start folic acid tablets several days before your first infusion, as instructed by your team. You will also receive a vitamin B12 injection before treatment begins. Both continue throughout the regimen.
Pre-cycle blood tests
Kidney function and blood counts are checked before each cycle. Results confirm whether the cycle can proceed on schedule. A delay is a safety step, not a sign the treatment is not working.
Pre-medications on the day
Before the infusion you receive anti-nausea medicine and dexamethasone. The steroid is given specifically to reduce the skin rash that pemetrexed can cause.
Pemetrexed infusion
Pemetrexed is given first, intravenously, over a short period. Your nurse will confirm the expected duration for your infusion.
Cisplatin infusion with hydration
Cisplatin follows, with intravenous fluids given alongside to protect the kidneys. This is the longest part of the session.
Observation and discharge
After the infusion you remain for a period of observation. When your team is satisfied, you are discharged. Arrange for someone to accompany you — do not drive yourself home.
Which lung cancers is this regimen used for?
This regimen is used for non-squamous non-small cell lung cancer — mainly adenocarcinoma, large cell carcinoma, and NSCLC where the histology has not been further classified.
Pemetrexed has limited effect in squamous cell carcinoma. Squamous tumours express high levels of the enzyme pemetrexed targets. NCCN and ESMO guidelines both restrict pemetrexed-based regimens to non-squamous histology on this basis.
Small cell lung cancer requires a different regimen entirely. If your report says SCLC, this page does not describe your treatment.
Who should not receive this regimen?
This regimen is not used for every lung cancer diagnosis. Eligibility is decided by an oncologist on the individual case.
Pemetrexed is not effective in squamous cell carcinoma of the lung. Squamous tumours express high levels of thymidylate synthase, the enzyme pemetrexed is designed to block. For that histology, pemetrexed-based regimens are not part of standard care according to NCCN and ESMO guidance.
- Squamous cell carcinoma of the lung
- Small cell lung cancer, which requires a different regimen entirely
- Significant kidney impairment — pemetrexed is cleared by the kidneys, and reduced kidney function affects its clearance and toxicity
- Inability to receive or tolerate the required folic acid and vitamin B12 supplementation protocol
- Pregnancy — both cisplatin and pemetrexed carry known teratogenic risk
- Severe bone marrow suppression that has not recovered from a prior treatment
Where cisplatin cannot be used due to kidney problems or other clinical reasons, carboplatin may be substituted. That substitution is a decision for the treating oncologist.
Why do you need folic acid and vitamin B12?
Pemetrexed blocks several enzymes in the folate pathway. That same mechanism can deplete the body's folate reserves and cause serious side effects — including severe drops in blood counts and painful mouth sores.
Folic acid replaces what the drug depletes. Vitamin B12 supports the same pathway from a different angle. ASCO and NCCN guidance describes these supplements as substantially reducing toxicity without reducing the anti-tumour effect of pemetrexed.
Missing doses is not a minor oversight. Tell your team immediately if you have not been able to take the folic acid as directed — before the next infusion, not after.
Before your first cycle: what you need to do
- Start folic acid tablets on the schedule your team gives you — not on the morning of your first infusion.
- Confirm your vitamin B12 injection is arranged before the first cycle begins.
- Tell your team about every NSAID painkiller you take, including ibuprofen, naproxen, and diclofenac.
- Tell your team about all herbal supplements, Ayurvedic preparations, and non-prescription medicines.
- Bring a complete list of your medicines to every appointment.
- Arrange for someone to accompany you on infusion days — sessions take several hours and you should not drive home.
Questions families ask about this regimen
What is the difference between cisplatin and carboplatin in this regimen?
Both are platinum drugs and both are paired with pemetrexed. Cisplatin is standard in fit patients. Carboplatin is substituted when kidney function is impaired, hearing is affected, or other factors make cisplatin harder to tolerate. If your plan says Carboplatin-Pemetrexed or Platinum-Pemetrexed, the vitamin protocol and pemetrexed component are the same.
Can I take ibuprofen or diclofenac while on this regimen?
Not without asking your oncology team first. NSAIDs — including ibuprofen, naproxen, and diclofenac — slow how quickly the kidneys clear pemetrexed, which raises its level in the body and increases the risk of serious side effects. Paracetamol is generally acceptable but confirm with your team before taking anything for pain.
What is maintenance pemetrexed?
After the planned cycles of cisplatin-pemetrexed, some patients whose disease has not progressed continue on pemetrexed alone. This maintenance phase uses the same infusion pathway and the same vitamin supplementation protocol. Not all patients are candidates; your oncologist will discuss whether it applies to you after the initial cycles are reviewed.
Which side effects should I report the same day?
Tell your team the same day for any fever, shivering, severe nausea that stops you drinking fluids, a significant change in how much urine you pass, chest pain, or breathlessness. Also report severe mouth sores and any new hearing changes — cisplatin can affect hearing and early reporting matters. Do not wait for your next scheduled appointment.
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Frequently asked questions
Why is this regimen not used for squamous cell lung cancer?
Squamous tumours in the lung express high levels of thymidylate synthase — the main enzyme pemetrexed is designed to inhibit. When that enzyme is overexpressed, pemetrexed has limited effect. NCCN and ESMO guidelines restrict pemetrexed-based regimens to non-squamous non-small cell lung cancer on this basis. If your diagnosis is squamous cell carcinoma, your oncologist will discuss a different regimen.
Can I take a vitamin B12 tablet instead of having an injection?
The injection delivers a reliable dose without depending on gut absorption. The protocol requires an adequate and consistent B12 level to be established before pemetrexed is first given. A tablet does not guarantee that in the same way. Do not substitute or skip the injection without your team's instruction. Ask your team directly if you have concerns about having the injection.
What happens if I forget to take the folic acid?
Tell your team before the next infusion. A missed day is unlikely to cause immediate harm, but consistently low folate during pemetrexed treatment significantly raises the risk of severe bone marrow suppression and mouth sores. Your team will check whether your level is adequate before proceeding. Do not take extra tablets to catch up without being told to.
My chart says Platinum-Pemetrexed, not Cisplatin-Pemetrexed — is it a different treatment?
No. Platinum-Pemetrexed is the broader term for the regimen, used when carboplatin is the platinum drug or when the specific drug has not yet been confirmed. Both cisplatin and carboplatin are platinum compounds. The pemetrexed component and the vitamin protocol are the same whichever platinum drug is used.
Can this regimen be combined with immunotherapy?
In some patients with non-squamous NSCLC, a checkpoint inhibitor is added to platinum-pemetrexed as first-line treatment. This depends on your PD-L1 result, your fitness, and whether your tumour carries a driver mutation — targeted therapy takes precedence when an actionable mutation is found. Your oncologist will explain which approach is appropriate for your specific case.
How many cycles will I receive?
A typical course runs for several cycles, reviewed after each scan. The number depends on how the disease is responding, how well you are tolerating treatment, and whether maintenance pemetrexed is planned after the platinum phase. Your oncologist will give you the initial plan before the first cycle and revisit it as scan results come in. Cycle count is a plan, not a fixed number.
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