Find information on thousands of medical conditions and prescription drugs.

Cyclophosphamide

Cyclophosphamide is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity. more...

Home

Caduet

Calan

Campath

Capoten

Cardura

Casodex

Cathine

Ceclor

Cefotan

Cefzil

Celexa

Cerebyx

Chenodeoxycholic acid

Cholac

Choriogonadotropin alfa

Chorionic gonadotropin

Cialis

Cipro

Climara

Clomid

Colyte

Commit

Coreg

Corgard

Cotrim

Cozaar

Crestor

Cylert

Cytotec

Uses

The main use of cyclophosphamide is together with other chemotherapy agents in the treatment of lymphomas, some forms of leukemia and some solid tumors.

In addition, its use is becoming more common in autoimmune diseases where disease-modifying antirheumatic drugs (DMARDs) have been ineffective. Systemic lupus erythematosus (SLE) with severe lupus nephritis, for example, may respond to pulsed cyclophosphamide.

Pharmacokinetics

Cyclophosphamide is converted by mixed function oxidase enzymes in the liver to active metabolites. The main active metabolite is 4-hydroxycyclophosphamide. 4-hydroxycyclophosphamide exists in equilibrium with its tautomer, aldophosphamide. Most of the aldophosphamide is oxidised by the enzyme aldehyde dehydrogenase (ALDH) to make carboxyphosphamide. A small proportion of aldophosphamide is converted into phosphoramide mustard and acrolein. Acrolein is toxic to the bladder epithelium and can lead to hemorrhagic cystitis. This can be prevented through the use of aggressive hydration and/or Mesna.

Mode of action

The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells which have low levels of aldehyde dehydrogenase.

Phosphoramide mustard forms DNA crosslinks between and within DNA strands. This leads to cell death.

Cyclophosphamide has relatively little typical chemotherapy toxicity, as ALDH is present in relatively large concentrations in bone marrow stem cells, liver and intestinal epithelium, protecting these tissues against phosphoramide mustard.

Side-effects

Side-effects include chemotherapy-induced nausea and vomiting (CINV), bone marrow suppression, alopecia (hair loss) and lethargy. Hemorrhagic cystitis is a frequent complication, but this is prevented by adequate fluid intake and Mesna (sodium 2-mercaptoethane sulfonate). Mesna is a sulfhydryl donor and binds acrolein.

Cyclophosphamide is itself carcinogenic, potentially causing transitional cell carcinoma of the bladder as a long-term complication.

History

Cyclophosphamide and the related nitrogen mustard-derived alkylating agent ifosfamide were developed by Norbert Brock and ASTA (now Baxter Oncology). They converted the base nitrogen mustard into a non-toxic "transport form". This transport form was a pro-drug, subsequently actively transported into the cancer cells. Once in the cells, the pro-drug was enzymatically converted into the active, toxic form. Brock and his team synthesised more than 1,000 candidate oxazophosphorine compounds, eventually finding the drug cyclophosphamide (Brock 1996).

Read more at Wikipedia.org

• [List your site here Free!]

Total-body irradiation, cyclophosphamide, and stem cell transplantation in treating patients with hematologic cancer - Clinical Trial Review
From Journal of Drugs in Dermatology, 8/1/03

Sponsored by: Fred Hutchinson Cancer Research Center and National Cancer Institute (NCI)

RATIONALE: Adjusting the dose of drugs used in chemotherapy such as cyclophosphamide may decrease side effects while stopping cancer cells from dividing so they stop growing or die Radiation therapy uses high-energy x-rays to damage cancer cells Stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells

PURPOSE: Phase I trial to study the effectiveness of dose-adjusted cyclophosphamide combined with total-body irradiation and donor stem cell transplantation in treating patients who have hematologic cancer

Study Type: Interventional

Study Design: Treatment

OBJECTIVES:

* Determine a safe and reproducible method of adjusting the dose of cyclophosphamide based on its metabolism when given in combination with total body irradiation and hematopoietic stem cell transplantation in patients with hematologic malignancy.

OUTLINE:

* Preparative regimen: Patients undergo total body irradiation twice daily on days -6 to -4. Patients then receive dose-adjusted (based on metabolism) cyclophosphamide IV over 1 hour on days -3 and -2.

* Hematopoietic stem cell (HSC) infusion: Patients undergo allogeneic HSC transplantation on day 0. Patients receive graft-versus-host disease prophylaxis, CNS prophylaxis, and testicular irradiation as per institutional standard practices.

Patients are followed at days 28 and 75 and then regularly thereafter for survival.

Ages eligible for study: 18 years - 65 years, both genders

Inclusion Criteria:

DIAGNOSIS OF HEMATOLOGICAL MALIGNANCY, INCLUDING ANY OF THE FOLLOWING:

* Chronic myeloid leukemia

* Acute myeloid leukemia

* Acute lymphocytic leukemia

* Myelodysplastic syndromes

* Lymphoma

* Unlikely to respond to conventional treatment and would benefit from hematopoietic stem cell transplantation

* No bulky tumor mass requiring additional involved field radiotherapy

* No large body burden of tumor cells requiring cytoreductive chemotherapy before total body irradiation and cyclophosphamide

* Undergoing conditioning for transplantation at the University of Washington Medical Center

* Availability of 1 of the following types of allogeneic donors:

* HLA-identical family members

* Unrelated donors

* Allele match (match grade 1)

* One allele mismatch for A, B, C, DRB1 or DQB1 (match grades 2.1 or 2.2)

* Patient Characteristics:

* Life expectancy

* Not severely limited by diseases other than malignancy

* Not moribund

Hepatic

* Bilirubin no greater than 1.2 mg/dL

* No cirrhosis

* No hepatic fibrosis with bridging

Renal

* Creatinine no greater than 1.2 mg/dL

Cardiovascular

* No coronary artery disease

* No congestive heart failure requiring therapy

Pulmonary

* Oxygen saturation at least 93% (on room air)

Other

* Not pregnant or nursing

* Fertile patients must use effective contraception

* HIV negative

* No concurrent infection requiring systemic antibiotic or antifungal therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior hematopoietic stem cell transplantation

Radiotherapy

* No prior radiotherapy to the liver or adjacent organs

Other

* No concurrent aspirin or nonsteroidal anti-inflammatory medications such as ibuprofen (e.g., Motrinr or Advilr)

* No other concurrent phase I study enrollment

Location and Contact Information

Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109-1024, United States; George B. McDonald, MD, Study Chair, Fred Hutchinson Cancer Research Center Tel: 206-667-6932

Washington

A total of 20 patients will be accrued for this study.

Study ID Numbers CDR0000304522; FHCRC-1797.00

NLM Identifier NCT00062140

Return to Cyclophosphamide

Home

Contact

Resources

Exchange Links

ebay