How much Cytoxan is too much?

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Cytoxan is a very potent but also potentially toxic medication used for a variety of immune-mediated (and nephrology-relevant) diseases. It is often classified as a “cytotoxic agent”, as it works as an alkylating agent that explains its utility also as a chemotherapeutic agent.

Because it is traditionally used at very high doses in oncology as compared with nephrology, the risk of side effects is dramatically increased in oncology patients. However, the risk of malignancy–most notably bladder cancer, but also leukemias and non-melanoma skin cancers–is still present in nephrology patients treated for conditions such as lupus nephritis or ANCA-associated vasculitis. How can you minimize this risk?

A 2008 study by Faurschou et al looked at a cohort of 293 patients diagnosed with Wegener’s granulomatosis, many of which were treated with cyclophosphamide. They found that the risk of bladder cancer or leukemias was elevated for those explosed to a cumulative dose greater than 36 grams, but there was no increased risk of either cancer for those with a cumulative dose less than 36 grams. A cumulative dose of 36 grams would correspond to taking Cytoxan 100mg a day for 1 year. The authors also report that patients developed bladder cancer between 6.9 – 18.5 years after cyclophosphamide exposure.
One strategy for giving Cytoxan in Wegener’s that I have seen used quite often is giving Cytoxan and prednisone when the disease is initially diagnosed for a period of 6 months–then transitioning to, say, steroids and azathioprine. This way, the Cytoxan can be used to get the disease under relative control without causing the dramatically increased risk in cancers, and still could be used a 2nd time if there is another serious flare in the future. Also, because the appearance of cancer is relatively delayed, one may be less hesitant to use Cytoxan for longer periods of time in the elderly.

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