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Cytoxan (Cyclophosphamide)

Cytoxan is the brand name of a chemotherapy drug called cyclophosphamide. This drug has been used to treat cancer and other illnesses for decades. Cytoxan was first approved by the U.S. Food and Drug Administration (FDA) in 1959. Although not officially approved for any type of mesothelioma, doctors may prescribe this chemotherapy drug for patients battling this cancer.

Research and clinical trials show great promise that cytoxan can extend the lives of mesothelioma patients when combined with other chemotherapeutic agents. However, there are risks associated with this drug, including an increased risk of developing other cancers.

What is Cyclophosphamide?

Cyclophosphamide is manufactured by Baxter Healthcare Corporation and Bristol-Myers Squibb and is distributed under the name Cytoxan. Other companies, including Roxane Laboratories, make and distribute it as the generic drug cyclophosphamide. It comes in both tablet and intravenous forms.

The FDA first approved cyclophosphamide in 1959, and it is currently approved for treating several malignancies. These include several lymphoma types, multiple myeloma, neuroblastoma, ovary adenocarcinoma, breast carcinoma, retinoblastoma, and leukemia. Cyclophosphamide is also approved for use in pediatric patients with a condition called nephrotic syndrome. This condition does not generally respond well to other treatments.

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.  Cyclophosphamide 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 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 used in tablet form.

Common Side Effects

Cyclophosphamide causes side effects similar to those caused by other chemotherapy drugs. These side effects are include hair loss, fever, nausea, diarrhea, vomiting, loss of appetite, weight loss, and mouth and tongue sores.

Cytoxan also reduces the amount of white blood cells in the body. White blood cells are the fighters of the immune system. Therefore, patients receiving this treatment are more prone to infections. Patients taking cytoxan must be monitored for infections.

In some cases, the drug may cause severe immunosuppression, leading to bone marrow failure and possible life-threatening infections.

Other Side Effects

There are more serious side effects of Cytoxan, though they are less common. These include toxicity in 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. This can lead to heart infections, congestive heart failure, and arrhythmias. Pulmonary infections and respiratory failure are also possible.

Cyclophosphamide can cause serious birth defects, so it is contraindicated for women who are pregnant or may become pregnant.

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 caner. 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.

Cyclophosphamide Chemotherapy Combinations for Pleural Mesothelioma

While Cytoxan is not FDA approved for for treating mesothelioma, it has been used during clinical trials to determine safety and effectiveness. Some results are promising. Others show poor results, however research is ongoing.

One study involved 47 patients with pleural mesothelioma given radiation therapy. Some patients were then given chemotherapy with a combination of cyclophosphamide and doxorubicin. Others in the trial only received radiation therapy. Results showed those patients receiving the combination of chemotherapy drugs saw reductions in tumor size. These patients had an average survival time of 13 months. The survival time of patients who did not receive the chemotherapy drugs was only six months.

In another study, patients were given a triple combination of chemotherapy drugs. This combination included cyclophosphamide, doxorubicin, and platinum-based drugs, like cisplatin or carboplatin. Unfortunately, this combination did not prove successful. The progression-free survival time, the time from treatment until the cancer began to spread again, was less than two months. This is compared to 12 months for mesothelioma patients treated with the platinum-based drugs and pemetrexed, another chemotherapy drug.

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 drug called SS1P. Yet another trial is combining cyclophosphamide with vaccine therapies. Many of these studies are recruiting eligible mesothelioma patients. These trials lead the way in treatment, providing patients with access to experimental new treatments.

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 Edited by Dave Foster

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Dave has been a mesothelioma Patient Advocate for over 10 years. He consistently attends all major national and international mesothelioma meetings. In doing so, he is able to stay on top of the latest treatments, clinical trials, and research results. He also personally meets with mesothelioma patients and their families and connects them with the best medical specialists and legal representatives available. Connect with Patient Advocate Dave Foster

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