Cyclophosphamide

What is the risk of bladder toxicity from CYC?

Uses

FDA Approved

Off-label

Lupus nephritis

Dosed IV 1 gram per m2; oral 2 mg per kg

Polyarteritis Nodosa

Oral 2 mg per kg. 

Brand names

Cytoxan

Side effects

Infection

Hemorrhagic cystitis

Bladder cancer

Preventing complications

Hydration 

 CYC tablets should be administered in the morning and the patient advised to drink liberal quantities of fluid throughout the day (eight 8-ounce glasses of water or 2 liters are recommended). Patients should also attempt to empty their bladders before going to sleep. These measures decrease the time the bladder is exposed to the toxic metabolite acrolein. 

Use of Mesna 

Do not use Mesna for patients on oral CYC based on the expense, inconvenience, terrible taste, and lack of evidence for a protective effect. Daily oral administration of Mesna during daily CYC administration has been reported, but other experts do not use daily Mesna.

Monitoring

For patients on CYC, regular and frequent laboratory evaluations are required to screen for bone marrow toxicity, monitor renal function, and avoid major drug-induced bladder complications. 

Blood counts and differential – Complete blood counts (CBC) with differential should be obtained frequently. As an example, we repeat cell counts and differential every two weeks for as long as the patient is on CYC. Some clinicians may measure a CBC and differential every four weeks once patients have been on a stable dose of oral CYC. Total white blood cell counts of less than 3500/mm3 or an absolute neutrophil count (ANC) <1500/mm3 should lead to dose reductions, because lower counts are associated with a markedly increased risk of opportunistic infection.

Isolated lymphopenia, an anticipated effect although not a goal of therapy, does not indicate a need for altering the CYC dose.Marked lymphopenia is common during CYC therapy and is not a major cause for concern, as long as patients are also receiving routine P. jirovecii prophylaxis. However, the total white blood cell count should be maintained above 3500/mm3 and the dose reduced or held if leukopenia occurs. The goal of treatment is clinical improvement, which usually occurs without needing to induce leukopenia.