Key points
- Cyclophosphamide is an old, widely used chemotherapy drug that comes both as an injection and as tablets [1, 2].
- It is a core part of common combinations for breast cancer and lymphoma and is also used for leukaemia, myeloma and ovarian cancer [1, 3, 4].
- The main serious side effects: low blood counts and infection, and bladder damage (blood in the urine); drink plenty of fluids and pass urine often [1].
- Take the tablets in the morning and swallow them whole (do not chew or crush them) [2].
- Women should avoid pregnancy for 1 year and men for 4 months after treatment ends [1].
What is this drug and how does it work?
For physicians
Cyclophosphamide (brand names Endoxan and Cytoxan) is an alkylating agent. It is inactive itself (a prodrug) and is converted in the liver by cytochrome P450 enzymes to active metabolites; these probably cross-link tumour cell DNA and so interfere with the growth of rapidly proliferating cells [1]. One of its metabolites, acrolein, is excreted in the urine [1].
It was first approved in the United States in 1959 [1]. Cyclophosphamide is effective on its own but is mostly used with or after other anticancer drugs [1]. Besides cancer, it is also approved for some non-cancer conditions, such as minimal change nephrotic syndrome in children [1].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Breast cancer [1, 3]
- Early triple-negative breast cancer [5]
- Non-Hodgkin lymphoma (diffuse large B-cell lymphoma) [4, 6]
- Chronic lymphocytic leukaemia (CLL) [7]
- Preparation before CAR-T cell therapy [8, 10]
- Other blood cancers [1]
- Solid tumours [1]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Setting |
|---|---|
| Breast cancer | Adjuvant or preoperative treatment in regimens such as AC and CMF [1, 3] |
| Early triple-negative breast cancer | Neoadjuvant: AC or EC with pembrolizumab [5] |
| Non-Hodgkin lymphoma (diffuse large B-cell lymphoma) | R-CHOP or Pola-R-CHP regimen [4, 6] |
| Chronic lymphocytic leukaemia (CLL) | FCR regimen (fludarabine, cyclophosphamide and rituximab) [7] |
| Preparation before CAR-T cell therapy | With fludarabine, before the CAR-T cell infusion [8, 10] |
| Other blood cancers | Hodgkin lymphoma, multiple myeloma, acute and chronic leukaemias, advanced mycosis fungoides [1] |
| Solid tumours | Ovarian cancer, breast cancer, disseminated neuroblastoma and retinoblastoma [1] |
CMF = cyclophosphamide, methotrexate and fluorouracil.
| Cancer | Key evidence |
|---|---|
| Breast cancer | EBCTCG: four cycles of AC and standard CMF were equivalent (RR 0.98); compared with no chemotherapy, the RR for breast cancer death was 0.78 with 4AC and 0.76 with CMF [3] |
| Early triple-negative breast cancer | KEYNOTE-522: pathological complete response 64.8% vs 51.2% [5] |
| Non-Hodgkin lymphoma (diffuse large B-cell lymphoma) | R-CHOP vs CHOP: complete response 76% vs 63% [4]; POLARIX: 2-year progression-free survival 76.7% vs 70.2% [6] |
| Chronic lymphocytic leukaemia (CLL) | CLL8: 3-year progression-free survival 65% vs 45% with FC; hazard ratio 0.56 [7] |
RR = ratio of breast cancer death rates.
How it is taken and dosing
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Treatment regimens and doses: index5 regimens
The injection is given at a treatment centre as an injection or infusion into a vein; to reduce side effects such as facial swelling, headache and a blocked nose, it should be given slowly [1]. The tablets (25 and 50 mg) are usually taken once a day; take them in the morning and swallow them whole, without chewing or crushing. The tablets are toxic to cells; avoid touching broken tablets and wash your hands straight away if you do [2].
With both forms, drink enough fluids and pass urine often during and just after treatment to lower the risk of bladder damage [1, 2]. The FDA label gives no specific advice for a missed dose [2]; if this happens, do not double the dose and contact your doctor or pharmacist. Your doctor decides how long treatment lasts, and you should not stop it on your own.
- Conditions to give: do not give with neutrophils ≤1500 per µL or platelets below 50,000. With serious infection, stop or reduce the dose. Consider G-CSF for primary and secondary prophylaxis [1].
- Contraindications: severe hypersensitivity to cyclophosphamide or its metabolites (cross-sensitivity with other alkylating agents is possible) and urinary outflow obstruction [1].
- Bladder protection: exclude or correct urinary obstruction before starting; give enough fluids (oral or IV) during or just after administration to promote diuresis and frequent bladder emptying; give preferably in the morning. Mesna has been used to prevent severe bladder toxicity. Severe haemorrhagic cystitis: stop the drug. Use with caution in active urinary tract infection [1].
- IV administration: for direct injection, reconstitute only with 0.9% sodium chloride (water for injection gives a hypotonic solution); slow injection reduces side effects such as facial swelling, headache and nasal congestion [1].
- Monitoring: CBC to guide dosing; urine sediment for red cells regularly; symptoms of cardiotoxicity (especially with risk factors or heart disease), pulmonary toxicity and hepatic veno-occlusive disease [1].
- Renal impairment: the label gives no fixed dose adjustment; with CLcr 10 to 24 mL/min, monitor for toxicity (AUC about 38% higher with CLcr 25 to 50 and about 77% higher with 10 to 24). The drug is dialysable; keep a consistent interval between dosing and dialysis [1].
- Severe hepatic impairment (bilirubin above 3 times the upper limit): conversion to the active metabolite is reduced; monitor for reduced effectiveness [1].
For physicians
Regimens and dosing
General FDA label doses (malignancies, adults and children)
Monotherapy in patients without blood count deficits; in combination regimens the dose follows the regimen
Monotherapy in patients without blood count deficits; in combination regimens the dose follows the regimen
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Initial course | |||
| Cyclophosphamide | 40 to 50 mg/kg in divided doses | IV | Over 2 to 5 days |
| Or | |||
| Cyclophosphamide | 10 to 15 mg/kg | IV | Every 7 to 10 days |
| Cyclophosphamide | 3 to 5 mg/kg | IV | Twice weekly |
| Oral | |||
| Cyclophosphamide | 1 to 5 mg/kg daily | Oral, in the morning | Initial and maintenance |
AC: doxorubicin + cyclophosphamide
Breast cancer, adjuvant (axillary node-positive)Cycle length: Every 21 days
Breast cancer, adjuvant (axillary node-positive)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Doxorubicin | 60 mg/m² | IV | Day 1 |
| Cyclophosphamide | 600 mg/m² | IV | Day 1 |
As per the doxorubicin label [9]; the same cyclophosphamide dose was used in KEYNOTE-522 (AC or EC) [5].
Evidence: KEYNOTE-522 (2020)
R-CHOP (cyclophosphamide component)
Diffuse large B-cell lymphomaCycle length: Every 21 days
Diffuse large B-cell lymphoma
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cyclophosphamide | 750 mg/m² | IV | Day 1 |
The same cyclophosphamide dose in Pola-R-CHP [6].
Evidence: POLARIX (2022)
FCR (CLL8 trial)
Chronic lymphocytic leukaemia, fit patients without prior treatmentCycle length: Every 28 days
Chronic lymphocytic leukaemia, fit patients without prior treatment
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Fludarabine | 25 mg/m² daily | IV | Days 1 to 3 |
| Cyclophosphamide | 250 mg/m² daily | IV | Days 1 to 3 |
| Rituximab | 375 mg/m² (day 0 of cycle 1), then 500 mg/m² (day 1 of cycles 2 to 6) | IV |
Doses from the CLL8 trial [7].
Evidence: CLL8 (2010)
Lymphodepletion before CAR-T (ZUMA-7)
Before axicabtagene ciloleucelCycle length: Once
Before axicabtagene ciloleucel
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cyclophosphamide | 500 mg/m² daily | IV | On the fifth, fourth and third days before the CAR-T infusion |
| Fludarabine | 30 mg/m² daily | IV | On the fifth, fourth and third days before the CAR-T infusion |
Doses and days as per the FDA label for axicabtagene ciloleucel (Yescarta) and the ZUMA-7 trial [8, 10]. Before starting lymphodepletion, make sure the patient's CAR-T product is available [10].
Evidence: ZUMA-7 (2023), ZUMA-7 (2022)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Side effects
For physicians
Common adverse reactions
According to the FDA label, the most common adverse reactions to cyclophosphamide are neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting and diarrhoea; the label gives no specific percentages for them [1]. White cell and platelet nadirs usually occur in the first and second weeks of treatment, and counts usually return to normal after about 20 days [1]. Other adverse reactions: stomatitis, amenorrhoea or irregular menses, early menopause and impaired wound healing [1].
For example, in 1492 women with breast cancer who received AC (doxorubicin 60 and cyclophosphamide 600 mg/m², 4 cycles), alopecia was reported in 92%, vomiting within the first 12 hours in 34% and vomiting beyond 12 hours in 37% [9]. These figures refer to the combination, not cyclophosphamide alone.
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Serious infection: a temperature of 38 °C or chills; old infections such as shingles, tuberculosis or hepatitis sometimes become active again [1].
- Bladder damage: blood in the urine or burning when passing urine; drink plenty of fluids and pass urine often [1].
- Heart problems, mostly with high doses: shortness of breath, palpitations or swollen legs [1].
- Lung damage, even years later: a new cough or shortness of breath [1].
- Infertility (sometimes permanent), harm to an unborn baby and a small rise in the risk of other cancers in later years [1].
For physicians
The FDA label for cyclophosphamide has no boxed warning but lists these important warnings [1]:
- Myelosuppression and immunosuppression: can lead to serious and sometimes fatal infections (including sepsis); latent infections such as viral hepatitis, tuberculosis and herpes zoster may reactivate [1].
- Urinary tract and renal toxicity: haemorrhagic cystitis, haematuria and, in severe cases, bladder ulceration or fibrosis, which can be fatal; urinary tract obstruction must be relieved before starting. Mesna has also been used to prevent severe bladder toxicity [1].
- Cardiotoxicity: myocarditis, pericarditis, pericardial effusion, arrhythmias and heart failure, especially with high doses, older age, prior cardiac radiotherapy or other cardiotoxic drugs [1].
- Pulmonary toxicity: pneumonitis and pulmonary fibrosis, which may develop even years after treatment [1].
- Secondary malignancies: urinary tract cancer, myelodysplastic syndrome, acute leukaemia, lymphoma, thyroid cancer and sarcoma [1].
- Hepatic veno-occlusive disease (VOD), especially with conditioning regimens for bone marrow transplantation [1].
- Embryo-fetal toxicity, infertility (permanent in some patients), impaired wound healing and hyponatraemia resembling SIADH [1].
The drug is contraindicated in patients with a history of severe hypersensitivity to cyclophosphamide and in urinary outflow obstruction [1].
When should I call my doctor?
Contact your treatment team or go to the emergency department straight away if you have [1]:
- Any fever or chills (check your temperature regularly)
- Pink or red urine, blood in the urine or urinary symptoms such as burning
- New or worsening shortness of breath or cough
- Swelling of the ankles or legs, palpitations, weight gain of more than about 2.3 kg (5 pounds) in 24 hours, dizziness or loss of consciousness
- A possible or confirmed pregnancy
Interactions, pregnancy and precautions
- Drug interactions: protease inhibitors (HIV medicines) may increase toxicity; use with metronidazole has been associated with acute encephalopathy and with tamoxifen with a higher risk of clots; the effect of warfarin may be reduced or increased, and ciclosporin levels may fall [1].
- Anaesthesia and surgery: if you have had cyclophosphamide within 10 days before a general anaesthetic, tell the anaesthetist; with depolarising muscle relaxants (such as suxamethonium) it may cause prolonged apnoea [1].
- Pregnancy: the drug can harm an unborn baby. A pregnancy test is needed before starting; women should use effective contraception during treatment and for 1 year after it ends, and men with a partner who could become pregnant for 4 months after treatment ends [1].
- Breastfeeding: the drug passes into breast milk; do not breastfeed during treatment and for 1 week after the last dose [1].
- Fertility: cyclophosphamide may cause infertility (sometimes permanent) in both sexes, and the risk of early menopause rises with age; talk about fertility preservation before treatment [1].
Frequently asked questions
Why do I have to drink a lot of fluids during treatment?
What should I do if my urine turns pink or red?
What is the difference between cyclophosphamide tablets and injections?
Will my hair fall out?
Scientific evidence
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Key studies
6 itemsAssessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Pembrolizumab for Early Triple-Negative Breast Cancer
Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma
Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma
Clinical guidelines
2 itemsBreast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer
Related cancer types
Treatment regimens (physicians)
References
10 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma
- 9
- 10
This page is based on reputable scientific sources and was last updated on 27 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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