In 2020 alone, cancer affected over 18 million people worldwide. There are various therapeutic approaches and many chemotherapy drugs used to treat cancer. Chemotherapy is one of the most common types of treatment prescribed for cancer patients. One specific chemotherapy drug is cyclophosphamide. Cytoxan is the brand name of cyclophosphamide. Continue reading to learn more about cyclophosphamide, how it works, what drugs to avoid while on it, and what possible side effects to expect.

Cyclophosphamide and its role in cancer treatment

Cyclophosphamide belongs to the class of alkylating agents and is an effective option for cancer treatment as it weakens and destroys cancerous cells by interfering with the cells’ genetic material. 

While cyclophosphamide is a valuable weapon against cancer, it also has various side effects and interactions with other medications. Talk to your doctor and other health care providers about what to expect when taking this drug. 

How does cyclophosphamide work against cancer cells?

Cyclophosphamide exerts its anticancer effects through the alkylation process. After administration into the body, it attacks the DNA of rapidly dividing cells like cancerous cells. Cyclophosphamide stops the growth of cancer cells by disrupting their ability to multiply. 

Role in inhibiting the growth of cancer cells

As mentioned, cyclophosphamide is one of the alkylating agents designed to stop the cells from making copies of themselves. In other words, these chemo drugs work by stopping the reproduction of the cells. Specifically, alkylating agents target cells' DNA material and damage it. 

To better understand how chemotherapy works, let’s talk about cell cycle. When a new cell is created in your body, it has to go through a process before becoming mature and functional. This process is called the cell cycle, which consists of different phases. 

Cyclophosphamide works in all phases of cell cycle and can be used for the treatment of different types of cancers. 

How does cyclophosphamide affect the immune system?

Chemotherapy is a powerful therapy that can be very effective in eradicating cancer, but it also puts the patient’s body through a lot of unpleasant adverse effects. One of the reasons is that chemotherapy drugs can’t distinguish between healthy cells and cancer cells. This would mean that when a person receives chemotherapy, their normal, healthy cells are damaged while the cancerous cells are being attacked. 

One of the unique properties of cyclophosphamide is that it can also work as an immunosuppressant. Immunosuppressants are agents that work to dampen the activity of the body’s immune system. At lower doses, cyclophosphamide selectively targets immune cells, specifically T cells or lymphocytes, a type of white blood cell. Cyclophosphamide reduces the numbers and activity of lymphocytes. In the case of autoimmune disease, this immunosuppressive effect is beneficial to prevent organ transplant rejection. It has been studied that the immunosuppressive action of cyclophosphamide can reduce the immune system's response to the tumor. In addition, due to its immunosuppressive properties, cyclophosphamide is used in severe cases of systemic lupus erythematosus (SLE), systemic sclerosis, some forms of vasculitis, and sometimes, this drug even has a role in treating rheumatoid arthritis (RA).  

How does it affect different types of cancer?

Cyclophosphamide is effective against various cancer types. Its efficacy depends on the disease or cancer stage and treatment goals. 

Breast cancer

In breast cancer, it is often combined with other chemotherapy drugs. It targets primary tumors and prevents the recurrence of cancerous cells. 

Lung cancer 

Cyclophosphamide is commonly used to improve treatment outcomes in small-cell lung cancer.

Multiple myeloma 

Multiple myeloma affects plasma cells in the bone marrow. Cyclophosphamide is combined with other therapeutic regimens and suppresses abnormal plasma cell growth.

Therapeutic uses

Cyclophosphamide is a potent cancer drug and is indicated for various medical conditions as follows:

Cancer treatment

Cyclophosphamide is commonly used to treat various types of cancers such as multiple myeloma, breast cancer, ovarian cancer, chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma, neuroblastoma, retinoblastoma, small cell lung cancer, and various types of sarcoma. It is often administered along with other chemotherapy agents to destroy cancerous cells and prevent their growth. 

Autoimmune diseases

Cyclophosphamide treats various autoimmune disorders like systemic lupus erythematosus (SLE), rheumatoid arthritis, vasculitis, and myasthenia gravis. Cyclophosphamide suppresses the immune response to these diseases.

Hematopoietic stem cell transplantation

A high dose of cyclophosphamide is given before a stem cell transplant. It helps to remove the patient's bone marrow cells. It allows the engraftment of transplanted stem cells.

Nephrotic syndrome

Nephrotic syndrome is a kidney disorder that happens due to excessive protein loss in the urine. Cyclophosphamide can be used to reduce inflammation in the kidneys and control the disease.

Immunosuppression

In some cases, cyclophosphamide suppresses the immune system before organ transplantation to prevent rejections.

Administration and dosage guidelines

Dosage forms

Cyclophosphamide is available in different dosage forms. The two main forms are oral tablets and intravenous (IV) injections (into a vein injection).

Tablets

Cyclophosphamide tablets are taken orally with water. The dose is dependent on the patient's body weight, health, and the specific cancer being treated.

Intravenous Injections

These are the preferred choice for the administration of cyclophosphamide. An injection containing the cancer drug is injected directly into the vein. It is typically given in a hospital or clinic setting to treat cancer.

Guidelines

The appropriate dosing frequency and treatment schedule for cyclophosphamide vary depending on several factors, including the stage and type of cancer. Comorbidity, prior medications, and concurrent medications influence the dosage and frequency of the drug.

Tell your doctor or health care professional about any pre-existing conditions you have and all the medicines you are taking, including non-prescription drugs and herbal supplements. Your doctor will closely monitor your reaction to the medication and will adjust the dosage as necessary. 

Intravenous injections should be administered in a controlled environment under medical supervision. Tell your doctor about any unusual or allergic reaction or side effects immediately.

Patients who receive oral cyclophosphamide tablets should strictly adhere to the dosage and treatment schedule prescribed by their healthcare team. Talk to your doctor about potential side effects to expect when cyclophosphamide is used.

Possible side effects and their management

Cyclophosphamide, like other cancer drugs, causes various side effects.

Common side effects

Infection

Similar to other cancer treatments, cyclophosphamide increases the risk of opportunistic infections. These are the types of infection that people with normal immune systems would not have any problems fighting off. This adverse effect can put cancer patients at risk for serious infections such as viral infection, fungal infection, or even tuberculosis. Inform your healthcare providers immediately if you experience any sign of infection, such as generalized malaise, fever, chills, cough, and weakness. 

Hair loss

Hair loss or thinning is the most common side effect during cyclophosphamide treatment. This can be an emotional experience for many patients. Be sure to find emotional support to help cope with changes in appearance. Careful brushing can help to slow the loss of hair during therapy.  

Sore throat

Cyclophosphamide can irritate the throat, causing discomfort or difficulty swallowing. Warm salt water solution gargles can help soothe a sore throat. Throat lozenges are also helpful in alleviating these symptoms. Avoid spicy or acidic foods to reduce the chances of throat irritation.

Gastrointestinal issues

Cyclophosphamide may affect the digestive system and cause nausea, vomiting, diarrhea or constipation, loss of appetite, etc. 

Communicate with your doctor and follow his advice to manage gastrointestinal side effects. Consider dietary supplements, stay well-hydrated, and take anti-nausea medications to alleviate these symptoms.

Bladder irritation and kidney injury

Cyclophosphamide can irritate the bladder, causing discomfort. In severe cases, blood in the urine can also be present while taking cyclophosphamide. To prevent bladder irritation, drink plenty of fluids because it will dilute the drug in the urine. If you experience difficulty passing urine or have brown urine while taking cyclophosphamide, your doctor may prescribe a drug called mesna to protect the bladder.

Blood-related side effects 

Anemia (low red blood cells count)

Another one of the common cyclophosphamide side effects is a decrease in red blood cells, causing anemia. A low blood cell count can lead to fatigue and weakness. Your health care provider may recommend dietary changes, iron supplements, or, in severe cases, a transfusion of red blood cells.

Low white blood cells count

Cyclophosphamide may reduce the body’s production of white blood cells. Low levels can increase your chances of infections. Patients should maintain good hand hygiene and avoid contact who have contagious diseases. Your doctor may consider administering growth factors to stimulate white blood cell production when necessary.

Blood count monitoring and regular blood tests

During cyclophosphamide treatment, regular blood tests are conducted to evaluate the blood cell counts. These tests help to adjust the dosage or treatment schedule. Patients should strictly adhere to the recommended blood test schedule and promptly inform of any serious symptoms. 

Allergic reactions 

Cyclophosphamide, like any medication, can cause unusual or allergic reactions. Stop taking cyclophosphamide and seek medical attention immediately if you experience any of the following signs of an allergic reaction: 

• Skin rash or hives 
• Swelling of the face, lips, tongue, or throat
• Difficulty breathing or shortness of breath

Administer epinephrine (if available) for severe allergic reactions with symptoms such as difficulty breathing and swelling. If an allergic reaction happens at home, you should call 911 immediately. Epinephrine should only be administered if prescribed by a health care provider. 

Uncommon side effects

• Fatigue
• Bleeding or bruising
• Fever and infection
• Irregular heartbeat or chest pain
• Sudden weight gain due to swelling of ankles, feet, and hands

What should you avoid taking while on Cyclophosphamide?

Cyclophosphamide may interact with other medicines and substances.

Interaction with other medicines

Cyclophosphamide can interact with live vaccines such as measles, mumps, and rubella (MMR), chicken pox, and yellow fever. It can also interact with other chemotherapy drugs like allopurinol, and herbal supplements like turmeric. 

Let your doctor know if you are currently taking any drugs such as chloramphenicol, chloroquine, digoxin, phenobarbital, phenothiazines, primidone, St John's wort, or voclosporin (Lupkynis), as these drugs can interact with cyclophosphamide.

Interaction with alcohol and dietary supplements

It’s recommended that you do not drink alcohol during cyclophosphamide treatment because it may cause certain side effects and interfere with the drug's activity. 

Consult your health care provider before taking any dietary supplements, as certain supplements containing antioxidants can interfere with the effectiveness of cyclophosphamide. 

Birth control use and cyclophosphamide therapy

Cyclophosphamide is not recommended to be used in pregnant women and nursing mothers. Women of childbearing age should use a reliable form of birth control while receiving cyclophosphamide treatment. You should inform your doctor immediately if you become pregnant while being on cyclophosphamide, as this drug can cause birth defects. Cyclophosphamide is excreted in breast milk and can be harmful to nursing infants. You should discuss with your healthcare provider if you are breastfeeding. 

When to seek medical attention

Cyclophosphamide, like many chemotherapy drugs, can sometimes cause severe life-threatening side effects that require immediate medical attention. 

Talk to your doctor and seek emergency medical care immediately if you notice the following symptoms and side effects:

• Difficulty breathing
• Swelling of the face or throat
• Rapid heartbeat
• A sudden drop in blood pressure
• High fever & chills (temperature above 100.4°F or 38°C)
• Severe headache & confusion
• Heavy nosebleeds
• Uncontrolled bleeding from cuts
• Blood in the urine or stool
• Severe chest pain or serious cardiac issue 

References:

• https://www.ncbi.nlm.nih.gov/books/NBK553087/
• https://www.sciencedirect.com/science/article/pii/S0006497120801293#:~:text=CYCLOPHOSPHAMIDE%20is%20a%20potent%20immunosuppressive,promote%20tolerance%20to%20several%20antigens.
• https://pubmed.ncbi.nlm.nih.gov/27646791/
• https://reference.medscape.com/drug/cytoxan-cyclophosphamide-342214
• https://ctep.cancer.gov/protocolDevelopment/docs/sideeffects/SideEffects-Cyclophosphamide.docx 
• https://www.cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer#:~:text=Incidence%20worldwide,of%20all%20cancers%20diagnosed%20worldwide.https://rheumatology.org/patients/cyclophosphamide-cytoxan
• https://www.researchgate.net/publication/308340449_The_effect_of_cyclophosphamide_on_the_immune_system_implications_for_clinical_cancer_therapy