Oral v. pulse intravenous cyclophosphamide : a retrospective analysis of adverse events in a setting with a high burden of infectious disease

Pretorius, Elmo ; Davids, Mogamat Razeen ; Du Toit, Riette (2015)

CITATION: Pretorius, E., Davids, M. R. & Du Toit, R. 2015. Oral v. pulse intravenous cyclophosphamide : a retrospective analysis of adverse events in a setting with a high burden of infectious disease. South African Medical Journal, 105(3):209-214, doi:10.7196/SAMJ.8785.

The original publication is available at http://www.samj.org.za

Article

Background. Cyclophosphamide (CPM) is still considered to be the first-line treatment for many life-threatening autoimmune conditions. It does, however, carry a significant risk of serious adverse events, especially infections. At present CPM is administered as either a daily oral dose (DOC) or an intravenous pulse (PIVC). There is uncertainty regarding the safety profiles of both regimens in settings with a high burden of infectious diseases. Objective. To compare the frequency and nature of adverse events related to the use of DOC and PIVC in such a setting. Methods. A cohort of patients treated with CPM for autoimmune diseases at Tygerberg Academic Hospital, Cape Town, South Africa, from 1 January 2008 to 31 May 2013 was studied. We compared participants receiving DOC and PIVC with regard to disease characteristics and the occurrence of major adverse events. Results. A total of 134 participants (92 DOC and 42 PIVC) were included. Participants in the DOC group were treated for longer (174 v. 101 days; p<0.01) and with higher cumulative doses (17 276 v. 3 327 mg; p<0.01). Risk of infection was similar in the two groups, although there were 6 deaths from leucopenic sepsis in the DOC group (v. 0; p=0.18). Nadir leucocyte counts were also lower in the DOC group (median 3.8 v. 5.3 × 109/L; p=0.02). Conclusion. Infection rates in the two groups were similar, but DOC was associated with longer treatment duration, greater cumulative CPM doses and more severe leucopenia. If resources allow and available literature provides support for efficacy, consideration should be given to greater use of PIVC.

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