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Cytoxan (Cyclophosphamide)

Cytoxan is the brand name of a chemotherapy drug called cyclophosphamide that has been in use for treating cancer and other illnesses for many decades. It was first approved by the U.S. Food and Drug Administration (FDA) in 1959 and is currently approved for treating many types of malignancies. Although it is not officially approved for any type of mesothelioma, doctors may prescribe this chemotherapy drugs for patients battling this cancer.

Recent studies and clinical trials have shown that there may be great promise for extending the lives of mesothelioma patients when cyclophosphamide is combined with other chemotherapeutic agents. There are some downsides to this drug, though, including the usual chemotherapy side effects but also an increased risk of developing other cancers.

What is Cyclophosphamide?

Cyclophosphamide is a drug that is manufactured by Baxter Healthcare Corporation and Bristol-Myers Squibb and distributed by Bristol-Myers Squibb 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 types of lymphomas, multiple myeloma, neuroblastoma, ovary adenocarcinoma, breast carcinoma, retinoblastoma, and leukemia. It is also approved for use in pediatric patients with a condition called nephrotic syndrome that does not respond well to other treatments.

How Cyclophosphamide Works

Cyclophosphamide is an alkylating agent, which is a type of cancer drug that interferes with the DNA in cells and prevents them from growing. It is also an immunosuppressant, which means that it impairs the functioning of the patient’s immune system. It is the immune system effect that makes this drug useful for treating nephrotic syndrome and autoimmune disorders. It is not approved for the latter, but doctors may prescribe cyclophosphamide to treat conditions like rheumatoid arthritis in which the patient’s immune system attacks healthy cells. As a chemotherapeutic agent, it is the alkylating effect that is of interest. Unlike many other chemotherapy drugs, Cytoxan does not have to be given intravenously; it can be used in tablet form.

Common Side Effects

Cyclophosphamide causes side effects that are similar to those caused by other chemotherapy drugs, and these are among the most common that patients experience when undergoing treatment: 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.

These are the cells of the immune system, so patients undergoing this treatment are more prone to infections. It is important for patients to be monitored for infections and white blood cells. In some cases the drug may cause severe immunosuppression that leads to bone marrow failure and possibly to infections that become life-threatening.

Other Side Effects

Less common, but still a concern are other more serious side effects of Cytoxan. These include toxicity in certain organs in the body, like the bladder and kidneys. This can cause bleeding and blood in the urine and kidney or bladder infections. In some patients, toxicity in the heart has also been reported, causing heart infections, congestive heart failure, and arrhythmias. Pulmonary infections and respiratory failure are also possible. Cyclophosphamide is contraindicated for women who are pregnant, as it can cause serious birth defects.

The Risk of Developing Other Cancers

One very serious potential side effect of being treated with cyclophosphamide is that ongoing and long-term treatment significantly increases the risk of developing secondary cancers. Some of the secondary cancers that have been reported include leukemia, lymphoma, sarcoma, thyroid cancer, myelodysplasia, and urinary tract caner. Screening for and preventing bladder infections may help prevent secondary bladder cancer. The possibility of developing another type of cancer is less of a concern for mesothelioma patients because the risk is balanced by the benefit of extending the lives of patients with this terminal cancer.

Cyclophosphamide Chemotherapy Combinations for Pleural Mesothelioma

While Cytoxan has never been approved by the FDA for treating mesothelioma, doctors and researchers have used it for these patients in clinical trials and studies to determine if it could be used effectively. Some of the results have been promising, while others show poor results, and many studies and trials are ongoing, providing new opportunities for treatment for struggling mesothelioma patients.

One study involved 47 patients with pleural mesothelioma were given radiation therapy. Some were then given chemotherapy treatment with a combination of cyclophosphamide and doxorubicin, while others only received radiation therapy. The results showed that those patients who got the combination of chemotherapy drugs saw reductions in tumor size and had an average survival time of 13 months. The survival time in the patients who did not get the chemotherapy drugs was only six months.

In another study patients were given a triple combination of chemotherapy drugs: cyclophosphamide, doxorubicin, and platinum-based drugs, like cisplatin or carboplatin. Unfortunately this combination did not prove to be 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 study 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 other drugs and after surgery 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. There are several clinical trials using cyclophosphamide and many of them are recruiting eligible mesothelioma patients. These trials are leading the way in treatment and provide patients with access to experimental new treatments.

Cytoxan is an old chemotherapy drug, but it is finding new life in treating conditions like mesothelioma. It has been proven for decades to help treat certain cancers like lymphomas, but now cyclophosphamide is being tested with the most difficult types of cancer to treat, like mesothelioma. While there are serious concerns, risks, and side effects, there is also a potential for great rewards with this drug, especially when combined with other treatments.

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