Cytoxan (cyclophosphamide)
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Cytoxan (cyclophosphamide) is a chemotherapy drug that has been used to treat cancer since its approval by the U.S. Food and Drug Administration (FDA) in 1959.[1] Although not approved for any type of mesothelioma, doctors may prescribe Cytoxan as part of treatment. Research and clinical trials show that Cytoxan can help control mesothelioma when combined with other chemotherapeutic agents in some patients.[2]
What is Cyclophosphamide?
Cyclophosphamide is manufactured by Baxter Healthcare Corporation and is distributed under the name Cytoxan.[1] Other companies, including Roxane Laboratories, make and distribute it as the generic drug cyclophosphamide. It comes in both tablet and intravenous forms.
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The FDA first approved cyclophosphamide in 1959, and it is currently approved for treating several malignancies. These include several lymphoma types, multiple myeloma, neuroblastoma, ovarian adenocarcinoma, breast carcinoma, retinoblastoma, and leukemia. Cyclophosphamide is also approved for use in pediatric patients with a condition called nephrotic syndrome, which often doesn’t respond well to other treatments.[1]
How Cyclophosphamide Works
Cyclophosphamide is an alkylating agent. This means it is a drug that interferes with cell DNA, preventing cells from growing and dividing. It is also an immunosuppressant, meaning it impairs the function of the immune system. The drug’s effects on the immune system make it useful for treating nephrotic syndrome and some autoimmune disorders, though it is not currently approved for the latter. As a chemotherapeutic agent, it is the alkylating effect that makes it effective. Unlike other chemotherapy drugs, Cytoxan does not have to be given intravenously; instead, it can be taken by mouth in capsule form.[1]
Common Side Effects
Cyclophosphamide causes side effects similar to those caused by other chemotherapy drugs. These side effects include hair loss, fever, nausea, diarrhea, vomiting, loss of appetite, weight loss, and mouth and tongue sores.[2]
Cytoxan also reduces the quantity of white blood cells in the body. White blood cells are a key component of the immune system; therefore, patients receiving this treatment can be more prone to infections and must be monitored closely.
Infrequently, the drug may cause severe immunosuppression, leading to bone marrow failure and possible life-threatening infections.[1]
Other Side Effects
There are more serious side effects of Cytoxan, though they are less common. These include toxicity for certain organs in the body, like the bladder and kidneys. Toxicity can cause bleeding and bladder infections. In some patients, toxicity in the heart has also been reported, which can lead to heart infections, congestive heart failure, and arrhythmias. Pulmonary infections and respiratory failure are also possible.[1]
Cyclophosphamide can cause serious birth defects, so it is contraindicated for women who are pregnant or may become pregnant.[1]
The Risk of Developing Other Cancers
Long-term treatment with cyclophosphamide significantly increases the risk of developing secondary cancers. Some secondary cancers that have been reported include leukemia, lymphoma, sarcoma, thyroid cancer, myelodysplasia, and urinary tract cancer.[2] Preventing and treating bladder infections can help prevent secondary bladder cancer. Developing a secondary cancer is less of a concern for mesothelioma patients because risk is balanced by the benefit, and secondary cancers can take many years to develop.
Cyclophosphamide Chemotherapy Combinations for Pleural Mesothelioma
While Cytoxan is not FDA approved for treating mesothelioma, it has been used in some clinical trials to determine its safety and effectiveness. Some results are promising, while others show poor results; however, research is ongoing.
One study involved forty-seven patients with pleural mesothelioma given radiation therapy. Some patients were then given chemotherapy with a combination of cyclophosphamide and doxorubicin in addition to the radiation therapy. The results showed those patients receiving the combination of chemotherapy drugs saw reductions in tumor size. These patients had an average survival time of thirteen months while the patients who did not receive the chemotherapy drugs averaged only six months.[3]
Clinical Trials
Mixed results notwithstanding, there are currently several clinical trials ongoing, near completion, or recruiting participants, that are using cyclophosphamide to treat pleural mesothelioma. One trial is using the drug in combination with surgery and other drugs to reduce tumor size. Another trial is using it with an experimental immunotoxin called SS1P.[4] Yet another trial is combining cyclophosphamide with vaccine therapies.[5] Many of these studies are recruiting eligible mesothelioma patients. These trials lead the way to discovering new treatments and providing patients with additional options.
Cytoxan is an old chemotherapy drug but is finding new life in treating conditions like mesothelioma. Proven for decades to help treat certain cancers, now cyclophosphamide is being tested with the most difficult types of cancer, including mesothelioma. While there are serious concerns, risks, and side effects, there is also a potential with this drug, especially when combined with other treatments.
Page Medically Reviewed and Edited by Kyle J. Becker, PharmD, MBA, BCOP
Kyle J. Becker, PharmD is certified by the Board of Pharmacy Specialties in Oncology Pharmacy. Dr. Becker earned his pharmacy degree from Shenandoah University and he currently serves as an oncology pharmacist at Parkview Cancer Institute.