Cyclophosphamide

Cyclophosphamide is a decades-old chemotherapy agent tried and tested for other cancers such as breast cancer, ovarian cancer and leukemia. For mesothelioma, however, it remains in the testing phases.

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This page features: 11 cited research articles

Researchers have already proven the safety and efficacy of cyclophosphamide in other diseases. The U.S. Food and Drug Administration (FDA) approved it for use in a number of cancers and diseases, including breast cancer and leukemia. Doctors have seen mixed results in clinical trials but remain hopeful that the drug can be implemented successfully in mesothelioma treatment regimens.

Now, researchers are studying its effects in combination with other chemotherapy drugs and in combination with immunotherapy on mesothelioma patients.

How Is It Used?

Unlike traditional chemotherapy drugs that must be administered intravenously, cyclophosphamide may also be administered in tablet form, once or twice daily. Mesothelioma patients in clinical trials usually receive the drug in the traditional intravenous manner, typically once every two weeks.

Cyclophosphamide is an alkylating agent, which means it is designed to inhibit tumor growth by interfering with the DNA of cancer cells. It can bind with DNA in mesothelioma cells. Once it does so, it prevents cell division and prompts the death of cancer cells.

In clinical trials, it is being studied in combination with other chemotherapy drugs or immunotherapy agents such as SS1P and certain vaccines.

Cyclophosphamide Information
Name Cytoxan
Related Drug Ifosfamide
Manufacturer Bristol-Myers Squibb
Dosage 40-50 mg/kg over 2-5 days
Administration Route Intravenous or oral
Active Ingredient Cyclophosphamide
Drug Class Antineoplastic alkylating agent
Medical Code J9097, J8530
Alternate Names Lyophilized Cytoxan, Endoxan, Cytophosphane, Neosar, Procytox, Revimmune, Cycloblastin
Interacting Drug Grapefruit, grapefruit juice, alcohol, live vaccines, carbamazepine, idarubicin, natalizumab, entanercept, palifermin, phenobarbital
Medical Studies Tumor-Infiltrating Lymphocytes and Low-Dose Interleukin-2 Therapy Following Cyclophosphamide and Fludarabine in Patients with Pleural Mesothelioma
FDA Warning Immune suppression, bone marrow toxicity, myelosuppression, kidney and urinary toxicity, heart toxicity, pulmonary toxicity, liver disease, secondary cancer, fetal toxicity, reproductive harm

What Are the Side Effects?

Cyclophosphamide comes with the general side effects of chemotherapy such as fatigue, weight loss, nausea and hair loss. It may cause additional side effects of abdominal pain, chest pain or shortness of breath, which usually are not severe.

However, doctors have noted one major potential side effect: an increased risk of other types of cancer. Long-term use and high doses create the greatest risk. Bladder cancer is the most common resulting cancer, which may develop years after use. Acute leukemia is also associated with the use of cyclophosphamide.

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Study Results

Researchers have had mixed results when testing cyclophosphamide in mesothelioma patients.

One study had positive results when patients underwent radiation therapy followed by a chemotherapy regimen of cyclophosphamide and doxorubicin. Adding the chemotherapy regimen caused tumors to decrease in size by about 25 percent. Overall, patients who received radiation therapy and chemotherapy survived a median of 13 months, as compared with only six months in patients who received radiotherapy alone. However, these results may be slightly skewed since chemotherapy was only given to those patients who were 70 or younger and who responded well to initial radiation therapy.

A study from 2010 combined cyclophosphamide with doxorubicin and platinum-based chemotherapy. Success was measured by progression-free survival, which is the amount of time that passes after treatment until the cancer spreads. In the three patients receiving this chemotherapy combination, median progression-free survival was only 1.5 months. This is significantly shorter than the median 12.3 months achieved by a regimen of pemetrexed and platinum-based chemotherapy.

A 2017 study combined cyclophosphamide with an immunotherapy approach known as T-cell therapy in six pleural mesothelioma patients. Of the four patients who were evaluable at publication, one showed tumor shrinkage, another’s tumor stopped growing and the other two did not respond (their cancer progressed). Researchers may continue to study it in future trials.

Doctors see promise in cyclophosphamide for the treatment of mesothelioma, and clinical trials continue to test the drug on mesothelioma patients. Ongoing studies are testing the chemotherapy agent in conjunction with immunotherapy or other chemotherapy drugs for use in treating mesothelioma patients.

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Last Modified September 24, 2018

Registered Nurse and Patient Advocate

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the regional director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Walter Pacheco, Managing Editor at Asbestos.com
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14 Cited Article Sources

  1. Aerts, J. (2011). Dendritic Cell-based Immunotherapy Combined with Low-dose Cyclophosphamide in Patients with Malignant Mesothelioma [Clinical Trial]. Erasmus Medical Center. Retrieved from: http://clinicaltrials.gov/ct2/show/NCT01241682
  2. American College of Rheumatology. (2010). Cyclophosphamide (Cytoxan). Retrieved from: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Cyclophosphamide-Cytoxan
  3. Anderson, T.M. (2011). Vaccine Therapy in Treating Patients with Stage I, Stage II, or Stage IIIA Non-small Cell Lung Cancer or with Stage I or Stage II Mesothelioma [Clinical Trial]. Roswell Park Cancer Institute. Retrieved from: http://www.clinicaltrials.gov/ct2/show/NCT00003974
  4. Kim, S.T. et al. (2010). The Efficacy of the Frontline Platinum-based Combination Chemotherapy in Malignant Peritoneal Mesothelioma. Japanese Journal of Clinical Oncology, 40(11), 1031-1036.   Retrieved from: https://academic.oup.com/jjco/article/40/11/1031/906872/The-Efficacy-of-the-Frontline-Platinum-based
  5. Linden, C.J., et al. (1996). Effect of hemithorax irradiation alone or combined with doxorubicin and cyclophosphamide in 47 pleural mesotheliomas: a nonrandomized phase II study. Retrieved from: http://erj.ersjournals.com/content/9/12/2565.full.pdf
  6. Medline Plus. (2011). Cyclophosphamide. Retrieved from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682080.html
  7. Medline Plus. (2011). Cyclophosphamide Injection. Retrieved from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a611044.html
  8. National Cancer Institute. (2011). Cancer Drug Information: Cyclophosphamide. Retrieved from: http://www.cancer.gov/cancertopics/druginfo/cyclophosphamide
  9. National Cancer Institute. (2011). Dictionary of Cancer Terms: alkylating agent. Retrieved from: http://www.cancer.gov/dictionary?cdrid=45589
  10. National Cancer Institute. (2011). NCI Drug Dictionary: Cyclophosphamide. Retrieved from: http://www.cancer.gov/drugdictionary?CdrID=39748
  11. National Cancer Institute. (2011). Pilot Study of Allogeneic Tumor Cell Vaccine with Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas [Clinical Trial]. Retrieved from: http://www.clinicaltrials.gov/ct2/show/NCT01143545
  12. National Cancer Institute. (2011). SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma [Clinical Trial]. Retrieved from: http://www.clinicaltrials.gov/ct2/show/NCT01362790
  13. Wiseman, C.L. (2009). Cyclophosphamide Plus Vaccine Therapy in Treating Patients with Advanced Cancer [Clinical Trial]. National Cancer Institute. Retrieved from: http://www.clinicaltrials.gov/ct2/show/NCT00002475
  14. Lee, S., et al. (2017). Phase 1/2 Trial of WT1 TCR-Transduced Central Memory and Naïve CD8+T Cells for Patients with Mesothelioma and Non-Small Cell Lung Cancer. Journal of Thoracic Oncology; 12(1):S1384-S1385. doi: 10.1016/j.jtho.2016.11.1962
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