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.
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.
What Is Cyclophosphamide Used for?
The FDA first approved cyclophosphamide in 1959, and it is currently approved for treating several malignancies. These include several types of lymphoma, 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]
Is Cyclophosphamide a Chemo Used for Mesothelioma?
Although it is not FDA-approved for mesothelioma, doctors can use Cytoxan/cyclophosphamide at their discretion. Although it is not a standard chemotherapy medication for mesothelioma, researchers continue to work with it to determine if it is safe or effective for patients.
Is Cytoxan a Strong Chemo Drug?
The name Cytoxan comes from the words for cell and toxic, which describes to some degree how damaging it can be. It is toxic to and kills cancer cells as well as many healthy cells. It has a long list of potential side effects, including those that can be severe or life-threatening.
Who Should Not Use Cyclophosphamide?
Your medical team will determine if cyclophosphamide is appropriate for you or if there are reasons you should not take it. Cyclophosphamide is contraindicated for anyone with a urinary obstruction.
How Cyclophosphamide Works
Cyclophosphamide is an alkylating agent, which means it 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.
How Is Cyclophosphamide Administered?
Unlike other chemotherapy drugs, Cytoxan does not have to be given intravenously. IV administration is one option for administering this drug to cancer patients.
Some patients can also take cyclophosphamide orally, in capsule or tablet form. It also comes in a powder used to make a solution.[1]
If taking cyclophosphamide orally, it is important to follow all your oncologist’s instructions. This might include taking in extra fluids, taking the medication in the morning, or taking it with food.
What Are the Side Effects of Cyclophosphamide?
Like other chemotherapy drugs, cyclophosphamide can cause many side effects. Because they target all fast-growing cells in the body, chemotherapy medications harm some healthy cells, resulting in side effects that range from uncomfortable to severe and debilitating.
Common Side Effects of Cyclophosphamide
Cyclophosphamide causes side effects similar to those caused by other chemotherapy drugs. These side effects include:[2]
- Hair loss
- Fever
- Nausea
- Diarrhea
- Vomiting
- Loss of appetite
- Weight loss
- Mouth and tongue sores
Cytoxan also reduces the number 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 closely monitored.
Infrequently, the drug may cause severe immunosuppression, leading to bone marrow failure and possibly life-threatening infections.[1]
Other Side Effects of Cyclophosphamide
Cytoxan has more serious side effects, though they are less common. These include toxicity to 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, leading 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 pregnant women 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 the benefit balances the risk, and secondary cancers can take many years to develop.
Can Cyclophosphamide Be Used to Treat 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.
Cyclophosphamide Chemotherapy with Radiation Therapy
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 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 those who did not receive the chemotherapy drugs averaged only six months.[3]
Cyclophosphamide with Immunotherapy
A study from 2017 combined cyclophosphamide with immunotherapy treatments that target an overexpressed tumor gene typical in mesothelioma patients. Although it was a small study, the researchers saw a good response in half of the patients.[4]
A promising type of immunotherapy treatment for mesothelioma and other cancers is CAR T-cell therapy. T cells are immune system cells. The therapy removes these cells from the patient, modifies them to bind to proteins on the cancer cells, and re-injects them into the patient. The modified T cells attack and kill cancer cells.
Cyclophosphamide is often used in advance of this type of immunotherapy to reduce the patient’s T-cell numbers. The purpose is to ensure that the body mostly utilizes the new, modified T-cells. Studies using this kind of therapy in mesothelioma patients have shown promising results.[5]
Clinical Trials with Cyclophosphamide
Mixed results notwithstanding, several clinical trials are currently underway or recently completed using cyclophosphamide to treat pleural mesothelioma. One trial used the drug in combination with surgery and other drugs to reduce tumor size.
Another trial used it with an experimental immunotoxin called SS1P.[6] Yet another trial combined cyclophosphamide with vaccine therapies.[7]
While some studies have concluded, others need eligible mesothelioma patients. One study in the recruiting phase is using cyclophosphamide with cord-blood natural killer cells and another chemotherapy drug.[8]
A clinical trial using cyclophosphamide along with an immunotherapy called CAR T-cell therapy is also recruiting. It involved altering a patient’s T-cells in the hope they would recognize and kill cancer cells. Results are not yet available.[9]
An ongoing trial of the SMARTEST protocol is currently recruiting qualified mesothelioma patients. This is an extension of the SMART protocol, which has shown great promise with mesothelioma patients and uses radiation followed by surgery.
In the current trial, patients receive cyclophosphamide followed by radiation therapy and then surgery. Some will also receive immunotherapy.[10]
Cytoxan is an old chemotherapy drug but is finding new life in treating conditions like mesothelioma. Proven for decades to help treat certain cancers, cyclophosphamide is being tested with the most difficult types of cancer, including mesothelioma. While there are serious concerns, risks, and side effects, this drug also has potential, especially when combined with other treatments.
