Cyclophosphamide

Definition

Cyclophosphamide is an anticancer (antineoplastic) agent. It also acts as a suppressor of the immune system. It is available under the brand names Cytoxan and Neosar.

Purpose

Cyclophosphamide is approved by the Food and Drug Administration (FDA) to treat several forms of cancer. These include:

• breast cancer
• leukemia
• malignant lymphoma
• multiple myeloma
• ovarian cancer
• soft tissue sarcoma
• mycosis fungoides
• nephrotic syndrome
• neuroblastoma
• Wilms' tumor
• retinoblastoma

Cyclophosphamide has activity against a wide variety of other cancers and conditions not specifically approved by the FDA, and patients should be aware that it may be commonly prescribed for these other disease states:

• bone cancer
• cervical cancer
• endometrial cancer
• germ cell tumors
• gestational trophoblastic tumors
• histiocytosis X
• lung cancer
• prostate cancer
• testicular cancer
• Wilms' tumor

Description

Cyclophosphamide chemically interferes with the synthesis of the genetic material (DNA and RNA) of cancer cells by cross-linking DNA strands, preventing these cells from being able to reproduce and continue the growth of the cancer.

Recommended dosage

Cyclophosphamide may be taken either orally (in pill form) or as an injection into the vein. The dosage prescribed may vary widely depending on the patient, the cancer being treated, and whether or not other medications are also being taken.

A typical oral dosage for adults is 1 to 5 mg per kg of body weight per day for initial and maintenance dose, or 400 to 1000 milligrams per squared meter of body surface area for four to five days every three to four weeks. A typical dosage by injection is 40 to 50 mg per kg, divided in several smaller doses, for two to five days. The dose for patients receiving bone marrow transplant may be as high as 60 mg per kg per day for two days.

Precautions

Cyclophosphamide should be taken on an empty stomach. If stomach irritation occurs, it should be taken with small amounts of food or milk. Cyclophosphamide should always be taken with plenty of fluids.

Cyclophosphamide can cause an allergic reaction in some people. Patients with a prior allergic reaction to cyclophosphamide should not receive this drug.

Cyclophosphamide can cause serious birth defects if either the man or the woman is taking this drug at the time of conception or if the woman is taking this drug during pregnancy. Contraceptive measures should be taken by both men and women while on this drug. Sterility is a common side effect of cyclophosphamide. This sterility is dependent upon the dose, duration of therapy, and state of function of the ovary or testicle at the time of administration of the drug. The sterility may be irreversible in some patients.

Because cyclophosphamide is easily passed from mother to child through breast milk, breast feeding is not recommended while under treatment.

Cyclophosphamide suppresses the immune system and interferes with the normal functioning of certain organs and tissues, and its excretion from the body is dependent on a normal functioning kidney and liver. For these reasons, it is important that the prescribing physician is aware of any of the following pre-existing medical conditions:

• a current case of, or recent exposure to, chicken pox
• herpes zoster (shingles)
• all current infections
• kidney disease
• liver disease
• a prior removal of one, or both, adrenal gland (s)

Also, because cyclophosphamide is such a potent immunosuppressant, patients taking this drug must exercise extreme caution to avoid contracting any new infections.

Side effects

Inflammation and irritation of the bladder, causing blood in the urine, is a common and severe side effect of cyclophosphamide. However, this side effect can be prevented and controlled with the administration of vigorous hydration with intravenous fluids before, during, and after chemotherapy. Patients should urinate frequently (at least every 2 hours) to enhance removal of the drug from the body, drink 3 to 4 liters of fluids a day while taking the drug by mouth and for 2 to 3 days after discontinuation of the drug unless otherwise instructed by the physician. Patients who are taking cyclophosphamide orally should avoid taking the drug at night so that they can go to the bathroom frequently during the day. The bladder-protectant drug mesna is usually administered if the patient is receiving more than 2, 000 mg per square meter of body surface area of the cyclophosphamide. Another common side effect of cyclophosphamide is increased susceptibility to infection due to decreased production of cells that fight infection. Increased risk of bleeding can occur due to decrease of platelets, which are involved with the clotting process. Decreased production of red blood cells can cause anemia and patients may experience fatigue, and shortness of breath.

Nausea and vomiting can occur, usually at the higher doses. Taking the appropriate antiemetics prescribed by the physician can prevent this side effect. Temporary hair loss (alopecia) usually begins 3-6 weeks after the start of therapy, but hair will regrow (although it may be a different color and/or texture). Sterility can occur in both men and women, and some women may also experience stoppage of menstruation. Diarrhea and ulcers of the mouth are also possible side effects of cyclophosphamide treatment.

Less common side effects include:

• nasal stuffiness
• runny eyes
• runny nose
• sinus congestion
• dizziness
• darkening of skin or fingernails
• skin rash
• sneezing (if the drug is given too rapidly by injection into the vein
• facial flushing

Some patients may also develop a second cancer years later with cyclophosphamide therapy alone or in combination with other anti cancer drugs. Patients should discuss this side effect with their physicians and determine the risks versus the benefits of this drug for treatment of the immediate cancer.

A doctor should be consulted immediately if the patient experiences any of the following:

• painful or difficult urination
• increase in frequency or feeling of urgency to urinate
• blood in the urine
• shortness of breath
• signs of infection such as cough, sore throat, fever and chills
• pain in the lower back or sides
• unusual bleeding or bruising
• blood in the stool
• tiny red dots on the skin
• delayed healing of any wounds
• skin rash
• yellowing of the skin or eyes

Interactions

Cyclophosphamide should not be taken in combination with any prescription drug, over-the-counter drug, or herbal remedy without prior consultation with a physician.

Paul A. Johnson, Ed.M.

Antineoplastic

—A drug that prevents the growth of a neoplasm by interfering with the maturation or proliferation of the cells of the neoplasm.

Neoplasm

—New abnormal growth of tissue.