Drug News

Cyclophosphamide and Ifosfamide

by Dr. Karen Albritton

There are a wide variety of drugs used in the treatment of sarcoma. In each issue, this column will briefly examine an existing or a new chemotherapy agent that is currently used for or is in a clinical trial for treating sarcoma. In previous issues of ESUN, I discussed vincristine and doxorubicin. This column deals with cyclophosfamide and ifosfamide. Cyclophosfamide is used with vincristine and doxorubicin.  Ifosfamide is usually used in alternating cycles with etoposide.

Cyclophosphamide (also known as cytoxan) is an alkylator agent, meaning it has a molecular structure that binds to DNA and creates a “cross-link” that blocks replication of the DNA.  It is available in an oral form but is usually given intravenously (through a small piece of tubing inserted into the patient's vein), either in a peripheral (arm) vein or a central line using a Hickman catheter, Broviac catheter, or a port-a-cath, over 1 hour. One of its breakdown products in the body causes a burn to the lining of the bladder, which can lead to bleeding into the urine, called hemorrhagic cystitis. This can be prevented by aggressive hydration and receiving a second protective drug called Mesna.  Mesna can be given IV or by mouth and should be taken for approximately twelve hours after a high dose of cyclophosphamide. Because cyclophosphamide kills some of the dividing cells in the bone marrow, it suppresses blood counts: low white blood cells make the immune system weak, low red blood cells (anemia) causes fatigue and short-windedness and can be treated with blood transfusions, and low platelets can increase bruising and bleeding and can be treated with transfusions. 

Cyclophosphamide usually causes nausea and vomiting; medicines to prevent and treat this should be given with the dose.  It also causes reversible hair loss.  In high cumulative doses, it can cause sterility. Men interested in preserving fertility should consider sperm banking before therapy begins.  Methods to preserve fertility in females are experimental; women with concerns should discuss this issue with their treating physician before therapy begins.  

Ifosfamide is also an alkylator. It is not available orally, so is given IV over 1-24 hours. It has all the potential side effects of cyclophosphamide listed above, and a few other unique side effects.  It can cause kidney damage, either resulting in poor function (as measured by a blood creatinine level or a functional study such as a nuclear glomerular filtration rate) or a problem called Fanconi’s syndrome, in which the kidneys do not properly regulate electrolytes. This is diagnosed by looking at the level of electrolytes (magnesium, phosphorus, bicarbonate, potassium, glucose). It can be temporary or permanent; oral replacement of “washed-out” electrolytes may be necessary. 

Because some of ifosfamide’s breakdown products cross into the brain, it can cause neurologic symptoms: encephalopathy (confusion, sleepiness, hallucination), or rarely seizure and coma.  These symptoms almost always resolve with discontinuation of the drug.  Patients who have mild to moderate symptoms can usually continue to receive the drug; symptoms are lessened if the Ifosfamide is given slower (over 24 hours) and other sedating drugs are avoided. 

You can find an informative tutorial on chemotherapy and other treatment procedures at the MEDLINEplus Interactive Health Tutorials website.