Cyclophosphamide therapy

Use of Enbrel in patients receiving concurrent cyclophosphamide therapy is not recommended... 

In 155 patients with Wegener s granulomatosis, of whom 142 took daily oral cyclophosphamide, the most frequent long-term cyclophosphamide-related adverse effects were cystitis despite mesna therapy (12%) and myelodysplasia (8%) (25). Patients who took a cumulative dose of over 100 g had a two-fold greater risk of cystitis and/or myelodysplasia than patients who took under 100 g. The authors emphasized that cyclophosphamide therapy should be as short as possible, with mesna and close surveillance in order to reduce treatment-associated morbidity. 

Squamous cell carcinoma of the bladder has been reported 4 years after pulsed cyclophosphamide therapy (50). However, the authors noted that other susceptibility factors, such as bladder diverticula and human papilloma virus infection, occurred in the intervening period and they speculated on the cumulative risk. 

It has been suggested that cyclophosphamide can contribute to the risk of cervical dysplasia. In a retrospective study of 110 patients with systemic lupus erythematosus, cervical dysplasia was significantly more frequent in patients who had received intravenous cyclophosphamide (10 of 61) than in a control group who did not receive cyclophosphamide (two of 49) (55). In addition, cervical pathology worsened during cyclophosphamide therapy in all four patients with pre-existing cervical dysplasia, and one patient developed in situ cervical carcinoma. 

Langford CA. Complications of cyclophosphamide therapy. Eur Arch Otorhinolaryngol 1997 254(2) 65-72. 

Buch RS, Schmidt M, Reichert TE. Akute Nekrose der Zunge unter Epirubicin-Cyclophosphamid-Therapie bei einem invasiv duktalen Mammakatzinom. [Acute tongue necrosis provoked by epirubicin-cyclophosphamide treatment for invasive ductal breast cancer.] Mund Kiefer Gesichtschir 2003 7(3) 175-9. 

Abuzarad H, Gadallah MF, Rabb H, Vermess M, Ramirez G. Emphysematous cystitis possible side-effect of cyclophosphamide therapy. Clin Nephrol 1998 50(6) 394-6. 

Mok CC, Lau CS, Wong RW. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum 1998 41(5) 831-7. 

Kattwinkel N, Cook L, Agnello V. Overwhelming fatal infection in a young woman after intravenous cyclophosphamide therapy for lupus nephritis. J Rheumatol 1991 18(1) 79-81. 

Rosenthal AK, Klausmeier M, Cronin ME, McLaughlin JK. Hepatic angiosarcoma occurring after cyclophosphamide therapy case report and review of the hterature. Am J Clin Oncol 2000 23(6) 581-3. 

When used in combination with corticosteroids, cyclophosphamide is dosed at 1-3 mg/kg for oral therapy and 0.5-1.0 g/m of body surface area for intravenous therapy. The most common route of cyclophosphamide administration is intravenous, although there is little evidence that this is better than oral administration. Likewise, there is no evidence to suggest the optimal duration of treatment. Based on empirical experience, cyclophosphamide generally is dosed monthly for 6 months and then every 3 months for a period of either 2 years or for 1 year after the nephritis is in remission." " Of course, cyclophosphamide therapy is not without risk. Serious toxic effects include suppression of hematopoiesis, opportunistic infections, bladder complications (e.g., hemorrhagic cystitis and cancer), sterility, and teratogenesis. White blood cell counts must be monitored during cyclophosphamide therapy, and if the nadir is less than 1500/mm, the dose must be adjusted to keep the white cell count above 1500/mm. Nausea and vomiting associated with cyclophosphamide can be controlled with oral ondansetron plus dexamethasone. ... 

Clearly, a complete evaluation for the presence of lung disease and pulmonary hypertension should be done so that appropriate therapy can be initiated early in the course of disease. Other rheumatologic conditions that may predispose to development of PAH are rheumatoid arthritis and systemic lupus erythematosus, especially in patients with Raynauds phenomenon. For patients in whom there is a reason to suspect acute inflammation or vasculitis, response to immunomodu-lation therapy may at least partially treat pulmonary hypertension (62). This may be particularly relevant in the lupus or mixed-connective tissue patient population. In particular, pulmonary hypertension also markedly improved in a series of patients who were responders to cyclophosphamide therapy. In the appropriate lupus patient who does not have fulminant systemic disease, one may have to consider lung biopsy to assess for inflammation and vasculitis. 

Genetic variations have not been found to effect nicotine metabolism (or plasma levels) [615, 616]. However, genetic variations in P450 2B6 have been associated with the outcome of cyclophosphamide therapy [617-619] and the doses of methadone used in addiction therapy... 

The Quantitation by Gas Chromatography-Chemical Ionization-Mass Spectrometry of Cyclophosphamide, Phosphoramide Mustard and Nor-nitrogen Mustard in the Plasma and Urine of Patients Receiving Cyclophosphamide Therapy Stable Isot., Proc. Int. Symp., 1977 (Pub. 1978) 97-106 CA 90 80439w Review... 

Collard HR, Ryu JH, Douglas WW, et al. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest 2004 125 2169-2174. 

Airo P, Danieh E, Parrinello G, et al. Intravenous cyclophosphamide therapy for systemic sclerosis. A single-center e q>erience and review of the literature with pooled analysis of lung function test results. Chn Exp Rheumatol 2004 22 573 578. 

Kirshon B, Wasserstrum N, Willis R, et al. Teratogenic effects of first-trimester cyclophosphamide therapy. Obstet Gynecol 1988 72 462 64. 

Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/ dermatomyositis. Rheumatology (Oxford) 2007 46 124—130. 

Odeh M. Renal cell carcinoma associated with cyclophosphamide therapy for Wegener s granulomatosis. Scand J Rheumatol 1996 25(6) 391-393. 

Faurschou M, Sorensen U, Mellemkjaer L, et al. Malignancies in Wegener s granulomatosis incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008 35(1) 100-105. 

Malayappan, B. et (2010) Quantitative high-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis of bis-N7-guanine DNA-DNA cross-links in white blood cells of cancer patients receiving cyclophosphamide therapy. Anal. Chem., 82 (9), 3650-3658. 

---