Prevention and Management of Intravesical BCG-related Lower Urinary Tract Symptoms

Summary

Common local side effects are generally seen during induction and during the first 6 months of BCG maintenance. BCG-related cystitis is frequent and unavoidable. Furthermore, repeated BCG instillation increases the incidence and severity of irritative bladder symptoms. Several methods attempted to reduce the intensity and frequency of BCG- related lower urinary tract symptoms (LUTS), such as, administration of anti-tuberculosis drug isoniazid or oral antibiotic ofloxacin or by reducing the BCG dose, but without any encouraging results. Local side effects requiring cessation of treatment are seen more frequently in the first year of therapy, preventing patients from receiving their BCG maintenance regimen. Pentosan Polysulphate (PPS), is an oral medication with unique analgesic properties used to relieve bladder pain and discomfort related to other conditions, has been investigated in a small study with encouraging result in this patient population. This suggest that PPS is well tolerated and effective at decreasing BCG-related LUTS. The purpose of this study is first to investigate the efficacy of co-administration of Pentosan Polysulphate to prevent these adverse events and the impact of this intervention on quality of life. The second goal is to determine which patients are more vulnerable to develop BCG- related lower urinary tract symptoms (LUTS), based on clinical assessment, demographics data, voiding parameters, and urinary inflammatory markers, and then to assess the effectiveness of BCG therapy following co-administration of ELMIRON.

Timeline

Start

2019-05-03

Primary completion

2022-02-15

Completion

2022-02-15

Outcome

Outcome not reported

Stopped: “Given the updated precautions on Elmiron as well as the risk benefit profile, we have decided to terminate the study.”

Publications

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• Background Anderson VR, Perry CM. Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis. Drugs. 2006;66(6):821-35. doi: 10.2165/00003495-200666060-00006.
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• Background Yadav S, Tomar V, Yadav SS, Priyadarshi S, Banerjee I. Role of oral pentosan polysulphate in the reduction of local side effects of BCG therapy in patients with non-muscle-invasive bladder cancer: a pilot study. BJU Int. 2016 Nov;118(5):758-762. doi: 10.1111/bju.13489. Epub 2016 Apr 23.
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• Background Chuang YC, Lee WC, Lee WC, Chiang PH. Intravesical liposome versus oral pentosan polysulfate for interstitial cystitis/painful bladder syndrome. J Urol. 2009 Oct;182(4):1393-400. doi: 10.1016/j.juro.2009.06.024. Epub 2009 Aug 15.
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• Background Abdo KM, Johnson JD, Nyska A. Toxicity and carcinogenicity of Elmiron in F344/N rats and B6C3F1 mice following 2 years of gavage administration. Arch Toxicol. 2003 Dec;77(12):702-11. doi: 10.1007/s00204-003-0472-9. Epub 2003 Sep 24.
• Background National Toxicology Program. NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies). Natl Toxicol Program Tech Rep Ser. 2006 Apr;(521):4-232.
• Background Kassouf W, Traboulsi SL, Kulkarni GS, Breau RH, Zlotta A, Fairey A, So A, Lacombe L, Rendon R, Aprikian AG, Siemens DR, Izawa JI, Black P. CUA guidelines on the management of non-muscle invasive bladder cancer. Can Urol Assoc J. 2015 Sep-Oct;9(9-10):E690-704. doi: 10.5489/cuaj.3320. Epub 2015 Oct 13. No abstract available.
• Background Nystrom E, Sjostrom M, Stenlund H, Samuelsson E. ICIQ symptom and quality of life instruments measure clinically relevant improvements in women with stress urinary incontinence. Neurourol Urodyn. 2015 Nov;34(8):747-51. doi: 10.1002/nau.22657. Epub 2014 Aug 22.

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