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CYCLOPHOSPHAMIDE INDUCED HEMORRHAGIC CYSTITIS SUCCESSFULLY TREATED WITH PENTOSANPOLYSULPHATE
0022-5347/05/1731-0103/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 173, 103, January 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000146626.78180.83
CYCLOPHOSPHAMIDE INDUCED HEMORRHAGIC CYSTITIS SUCCESSFULLY TREATED WITH PENTOSANPOLYSULPHATE PAUL J. TOREN
AND
RICHARD W. NORMAN*
From the Department of Urology, Dalhousie University, Halifax, Nova Scotia, Canada KEY WORDS: cyclophosphamide/adverse effects, cystitis/chemically induced, hemorrhage/etiology
Hemorrhagic cystitis is a well-known complication of cyclophosphamide (CYP) attributable to its active metabolite acrolein, which causes chemical irritation of the bladder epithelium.1 Although most cases resolve with discontinuation of the drug, some symptoms may persist for months. In some patients the cyclophosphamide effects cannot be stopped. Hemorrhage may necessitate transfusions or may lead to clots causing urinary retention. CASE REPORT
A 28-year-old male was diagnosed with Wegener’s granulomatosis in 1988 when he presented with pyoderma gangrenosum adjacent to the left orbit. The patient was treated successfully with 100 mg CYP daily but intermittent gross hematuria began to develop in 1993. The bleeding increased to the point that CYP was decreased to 50 mg daily for a few months in 1998 and then permanently in 2002. CYP had to be stopped temporarily for a few weeks in 1995 and 2002 because of increased degree of bleeding. When CYP was reinstituted the bleeding episodes recurred despite the dose decrease. The patient continued to pass clots on a weekly basis. The upper tracts were normal on ultrasound, and cystoscopy showed erythema and neovascularity. Blood evaluation in February 2002 revealed the patient was mildly anemic. He was started on 100 mg pentosanpolysulphate (PPS) 3 times daily. Within 3 months the hematuria stopped. He has continued on CYP and PPS, and the Wegener’s granulomatosis remains under good control. He has had no further hematuria for 18 months.
DISCUSSION
PPS, which is a semisynthetic glycosaminoglycan similar to heparin, is currently indicated for acute and maintenance treatment of patients with interstitial cystitis. It is orally administered, with a half-life of 4.4 hours for the unchanged drug, and about 3% to 5% of the drug is excreted in the urine. It is usually well tolerated. Since there is evidence that PPS is effective in treating hemorrhagic cystitis secondary to radiation, it was believed it might be useful in the management of CYP induced hemorrhagic cystitis.2, 3 In fact, PPS has been demonstrated to have a protective role against acrolein in animal studies,1 and there is a single report of its being useful for the treatment of CYP induced hemorrhagic cystitis.3 Complete control of hematuria was obtained in our patient, although hematuria returned whenever the medication was withdrawn. Several different acute treatments for CYP induced hemorrhagic cystitis are available, most commonly bladder irrigation and hydration. Prophylactically, mesna and saline diuresis are often used but require parenteral access. Our observed success treating CYP induced hemorrhagic cystitis with PPS offers further support for its safe and effective use in these difficult cases.
Submitted for publication June 15, 2004. * Correspondence: Queen Elizabeth II Health Sciences Centre, Victoria General Site, Victoria Building, 5 South, Room 293, 1278 Tower Rd., Halifax, Nova Scotia, B3H 2Y9, Canada (e-mail: [email protected]).
103
REFERENCES
1. Kalota, S. J., Stein, P. C. and Parsons, C. L.: Prevention of acrolein-induced bladder injury by pentosanpolysulfate. J Urol, 148: 163, 1992 2. Parsons, C. L.: Successful management of radiation cystitis with sodium pentosanpolysulfate. J Urol, 136: 813, 1986 3. Hampson, S. J. and Woodhouse, C. R.: Sodium pentosanpolysulphate in the management of haemorrhagic cystitis: experience with 14 patients. Eur Urol, 25: 40, 1994
Vol. 173, 103, January 2005 Printed in U.S.A.
DOI: 10.1097/01.ju.0000146626.78180.83
CYCLOPHOSPHAMIDE INDUCED HEMORRHAGIC CYSTITIS SUCCESSFULLY TREATED WITH PENTOSANPOLYSULPHATE PAUL J. TOREN
AND
RICHARD W. NORMAN*
From the Department of Urology, Dalhousie University, Halifax, Nova Scotia, Canada KEY WORDS: cyclophosphamide/adverse effects, cystitis/chemically induced, hemorrhage/etiology
Hemorrhagic cystitis is a well-known complication of cyclophosphamide (CYP) attributable to its active metabolite acrolein, which causes chemical irritation of the bladder epithelium.1 Although most cases resolve with discontinuation of the drug, some symptoms may persist for months. In some patients the cyclophosphamide effects cannot be stopped. Hemorrhage may necessitate transfusions or may lead to clots causing urinary retention. CASE REPORT
A 28-year-old male was diagnosed with Wegener’s granulomatosis in 1988 when he presented with pyoderma gangrenosum adjacent to the left orbit. The patient was treated successfully with 100 mg CYP daily but intermittent gross hematuria began to develop in 1993. The bleeding increased to the point that CYP was decreased to 50 mg daily for a few months in 1998 and then permanently in 2002. CYP had to be stopped temporarily for a few weeks in 1995 and 2002 because of increased degree of bleeding. When CYP was reinstituted the bleeding episodes recurred despite the dose decrease. The patient continued to pass clots on a weekly basis. The upper tracts were normal on ultrasound, and cystoscopy showed erythema and neovascularity. Blood evaluation in February 2002 revealed the patient was mildly anemic. He was started on 100 mg pentosanpolysulphate (PPS) 3 times daily. Within 3 months the hematuria stopped. He has continued on CYP and PPS, and the Wegener’s granulomatosis remains under good control. He has had no further hematuria for 18 months.
DISCUSSION
PPS, which is a semisynthetic glycosaminoglycan similar to heparin, is currently indicated for acute and maintenance treatment of patients with interstitial cystitis. It is orally administered, with a half-life of 4.4 hours for the unchanged drug, and about 3% to 5% of the drug is excreted in the urine. It is usually well tolerated. Since there is evidence that PPS is effective in treating hemorrhagic cystitis secondary to radiation, it was believed it might be useful in the management of CYP induced hemorrhagic cystitis.2, 3 In fact, PPS has been demonstrated to have a protective role against acrolein in animal studies,1 and there is a single report of its being useful for the treatment of CYP induced hemorrhagic cystitis.3 Complete control of hematuria was obtained in our patient, although hematuria returned whenever the medication was withdrawn. Several different acute treatments for CYP induced hemorrhagic cystitis are available, most commonly bladder irrigation and hydration. Prophylactically, mesna and saline diuresis are often used but require parenteral access. Our observed success treating CYP induced hemorrhagic cystitis with PPS offers further support for its safe and effective use in these difficult cases.
Submitted for publication June 15, 2004. * Correspondence: Queen Elizabeth II Health Sciences Centre, Victoria General Site, Victoria Building, 5 South, Room 293, 1278 Tower Rd., Halifax, Nova Scotia, B3H 2Y9, Canada (e-mail: [email protected]).
103
REFERENCES
1. Kalota, S. J., Stein, P. C. and Parsons, C. L.: Prevention of acrolein-induced bladder injury by pentosanpolysulfate. J Urol, 148: 163, 1992 2. Parsons, C. L.: Successful management of radiation cystitis with sodium pentosanpolysulfate. J Urol, 136: 813, 1986 3. Hampson, S. J. and Woodhouse, C. R.: Sodium pentosanpolysulphate in the management of haemorrhagic cystitis: experience with 14 patients. Eur Urol, 25: 40, 1994