Cyclophosphamide‐induced bladder toxicity in wegener's granulomatosis

Stillwell, Thomas J.; Benson, Ralph C.; DeRemee, Richard A.; McDonald, Thomas J.; Weiland, Louis H.

doi:10.1002/art.1780310402

Cited by 98 publications

(56 citation statements)

References 32 publications

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“…Although hemorrhagic cystitis is seen more frequently after intravenous administration, this distressing complication can be seen with oral cyclophosphamide as well, which is the usual mode of treatment in WG (15). Carcinoma of the urinary bladder is another serious, though less frequent, side effect.…”

Section: Regimens and Risksmentioning

confidence: 99%

The treatment of wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision?

DeRemee

1988

Arthritis & Rheumatism

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148

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Section: Regimens and Risksmentioning

confidence: 99%

The treatment of wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision?

DeRemee

1988

Arthritis & Rheumatism

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148

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Section: Conclusion Our Findings Indicate That Cyc Treatment Of Snv mentioning

confidence: 99%

“…In the setting of SNV, CYC-related urotoxicity has also raised concerns (13,14). In Wegener's granulomatosis (WG), an SNV frequently characterized by a chronic relapsing course requiring repeat treatment and for which CYC is a mainstay of therapy (15,16), elevated urinary tract cancer and/or hemorrhagic cystitis rates have been demonstrated in previous studies (13,14,(17)(18)(19)(20)(21)(22).…”

Section: Conclusion Our Findings Indicate That Cyc Treatment Of Snv mentioning

confidence: 99%

“…In Wegener's granulomatosis (WG), an SNV frequently characterized by a chronic relapsing course requiring repeat treatment and for which CYC is a mainstay of therapy (15,16), elevated urinary tract cancer and/or hemorrhagic cystitis rates have been demonstrated in previous studies (13,14,(17)(18)(19)(20)(21)(22). However, those studies showed wide variations in the frequency of urinary tract cancer and/or hemorrhagic cystitis, left unclear whether there is a cutoff dose below which cumulative CYC has no urotoxic effect, and did not provide information on CYC-related urotoxicity for SNV other than WG.…”

Section: Conclusion Our Findings Indicate That Cyc Treatment Of Snv mentioning

confidence: 99%

“…CYC-related urotoxicity includes hemorrhagic cystitis (3-5) and urinary tract cancers of the bladder (6,7) and, less commonly, the ureter and renal pelvis (8-10) that may occur long after the first CYC exposure (2). When CYC was used to treat nonHodgkin's lymphoma, cumulative 5-year hemorrhagic cystitis incidence rates of 12% and 12-year bladder cancer incidence rates of 11% (11) were reported, and the close link between cumulative CYC dose and secondary bladder cancer risk was established (12).In the setting of SNV, CYC-related urotoxicity has also raised concerns (13,14). In Wegener's granulomatosis (WG), an SNV frequently characterized by a chronic relapsing course requiring repeat treatment and for which CYC is a mainstay of therapy (15,16), elevated…”

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Incidence and predictors of urotoxic adverse events in cyclophosphamide‐treated patients with systemic necrotizing vasculitides

Guenno

Mahr

Pagnoux

et al. 2011

Arthritis & Rheumatism

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Objective. To assess hemorrhagic cystitis and urinary tract cancer incidence and predictors in cyclophosphamide (CYC)-treated patients with systemic necrotizing vasculitis (SNV).Methods. The French Vasculitis Study Group database, which contains longitudinal data on SNV patients, was searched for urinary tract cancer and/or hemorrhagic cystitis occurrences in patients diagnosed as having Wegener's granulomatosis (WG), microscopic polyangiitis, Churg-Strauss syndrome, or polyarteritis nodosa. The observed incidence of urinary tract cancer was compared to the expected incidence in the general population by calculating standardized incidence ratios (SIRs). Relationships between urinary tract cancer and/or hemorrhagic cystitis and 10 variables, including CYC dosage and administration route, were investigated by survival analyses for a nested subgroup of patients for whom detailed information on CYC exposure was available.Results. Among the 805 patients observed over 4,230 patient-years (mean followup 5.3 years), 22 cases of hemorrhagic cystitis and 7 of urinary tract cancer were identified in 27 patients. The SIRs for urinary tract cancer were 5.00 for all patients with SNV (P ‫؍‬ 0.001) and 5.96 for patients with WG (P ‫؍‬ 0.03). Based on 467 patients with detailed CYC information, cumulative CYC dose (hazard ratio [HR] for 10-gm increments 1.09; P ‫؍‬ 0.03), ever-oral CYC administration (HR 5.50; P ‫؍‬ 0.001), and WG (HR 2.96; P ‫؍‬ 0.01) independently predicted urinary tract cancer and/or hemorrhagic cystitis. According to univariate analyses, smoking (ever) (HR 8.20; P ‫؍‬ 0.02) and a prior hemorrhagic cystitis episode (HR 5.20; P ‫؍‬ 0.046) significantly predicted urinary tract cancer. Conclusion. Our findings indicate that CYC treatment of SNV is associated with a 5-fold higher risk of developing urinary tract cancer. Urotoxicity risk in SNV is associated with the cumulative CYC dose and its oral administration, and might be higher in WG.The alkylating agent cyclophosphamide (CYC) is a cytotoxic drug widely given, by either intravenous (IV) or oral routes of administration, to treat solid and hematologic malignancies (1) and rheumatic diseases, e.g., systemic lupus erythematosus, systemic sclerosis, or systemic necrotizing vasculitis (SNV) (2). It has long been recognized that CYC has substantial adverse effects, such as infections, secondary hematologic cancers, and urotoxicity. CYC-related urotoxicity includes hemorrhagic cystitis (3-5) and urinary tract cancers of the bladder (6,7) and, less commonly, the ureter and renal pelvis (8-10) that may occur long after the first CYC exposure (2). When CYC was used to treat nonHodgkin's lymphoma, cumulative 5-year hemorrhagic cystitis incidence rates of 12% and 12-year bladder cancer incidence rates of 11% (11) were reported, and the close link between cumulative CYC dose and secondary bladder cancer risk was established (12).In the setting of SNV, CYC-related urotoxicity has also raised concerns (13,14). In Wegener's granulomatosis (WG), an SNV frequently character...

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Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: Analysis of four prospective trials including 278 patients

Gayraud¹,

Guillevin²,

Toumelin³

et al. 2001

Arthritis & Rheumatism

473

151

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Objective To determine the long‐term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS), to compare the long‐term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae. Methods Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five‐Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis. Results The mean (±SD) followup of the entire population was 88.3 ± 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)–related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non–HBV‐related PAN who were given first‐line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores ≥2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001). Conclusion Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV‐related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first‐line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.

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Cyclophosphamide‐induced bladder toxicity in wegener's granulomatosis

Cited by 98 publications

References 32 publications

The treatment of wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision?

The treatment of wegener's granulomatosis with trimethoprim/sulfamethoxazole: illusion or vision?

Incidence and predictors of urotoxic adverse events in cyclophosphamide‐treated patients with systemic necrotizing vasculitides

Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: Analysis of four prospective trials including 278 patients

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