Bladder cyclophosphamide therapy

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. 

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. ... 

Anuria has occurred after silver nitrate irrigation for intractable bladder hemorrhage caused by cyclophosphamide chemotherapy (40). The level of obstruction was the ureterovesical junction on the one hand, and the collecting ducts of the renal papillae on the other. Therapy... 

Direct contact of the bladder epithelium with the catabolites acrolein and 4-hydroxy-cyclophosphamide is responsible for the hemorrhagic cystitis that can be a consequence of therapy with cyclophosphamide [78]. Aggressive hydration provides prophylaxis against this toxicity to the efferent urinary tract [79]. The sulfhydryl compound mesna has also demonstrated uroprotec-tive ability during therapy with cyclophosphamide [80]. Although hemorrhagic cystitis is a dose-related toxicity, chronic low doses of orally administered cyclophosphamide are also associated with development of this adverse event [81]. 

Drug therapy may also cause renal insufficiency due to lower urinary tract obstruction. Ureteral obstruction can be caused by calculi or retroperitoneal fibrosis. Bladder dysfunction with urinary outflow obstruction can result, particularly in males with prostatic hypertrophy, from anticholinergic drugs including tricyclic antidepressants and disopyramide. Bladder outlet and ureteral obstruction may result from bladder fibrosis following hemorrhagic cystitis with cyclophosphamide or ifosfamide therapy. Concurrent treatment with mesna can prevent cystitis and this complication. 

Fig. 9.14a, b. Bladder carcinoma treated with CISCA. a Pretreatment intravenous pyelography (IVP). Transitional cell carcinoma involving the bladder wall on the right, b Posttreatment IVP. After CISCA therapy, lA infusion with cisplatin and IV Cytoxan (cyclophosphamide) and Adriamycin (doxorubicin), revealed a complete response with a disappearance of the bladder tumor... 

---