Celecoxib for the Treatment of Non-muscle Invasive Bladder Cancer

Summary

The treatment of non-muscle invasive bladder cancer (NMIBC) is problematic given the variable natural history of the disease. Although contemporary treatment options are limited, new targets and new approaches are under investigation for preventing bladder cancer recurrence and progression. Among those, COX-2 is a promising target since plays an important role in urothelial carcinogenesis and iCOX-2 selective inhibitors, like celecoxib, effectively inhibit tumor development and growth and enhances survival, in bladder cancer in vitro and in vivo models. Therefore, the investigators conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC.

Timeline

Start

2003-03

Primary completion

2013-10

Completion

2014-01

Publications

• Background Arber N, Eagle CJ, Spicak J, Racz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B; PreSAP Trial Investigators. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med. 2006 Aug 31;355(9):885-95. doi: 10.1056/NEJMoa061652.
• Background Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET; APC Study Investigators. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. doi: 10.1056/NEJMoa061355.
• Background Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ; VIGOR Study Group. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528. doi: 10.1056/NEJM200011233432103.
• Background Colombel M, Saint F, Chopin D, Malavaud B, Nicolas L, Rischmann P. The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study. J Urol. 2006 Sep;176(3):935-9. doi: 10.1016/j.juro.2006.04.104.
• Background Dovedi SJ, Kirby JA, Davies BR, Leung H, Kelly JD. Celecoxib has potent antitumour effects as a single agent and in combination with BCG immunotherapy in a model of urothelial cell carcinoma. Eur Urol. 2008 Sep;54(3):621-30. doi: 10.1016/j.eururo.2008.01.013. Epub 2008 Jan 15.
• Background Grubbs CJ, Lubet RA, Koki AT, Leahy KM, Masferrer JL, Steele VE, Kelloff GJ, Hill DL, Seibert K. Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res. 2000 Oct 15;60(20):5599-602.
• Background Kilbridge KL, Kantoff P. Intravesical therapy for superficial bladder cancer: is it a wash? J Clin Oncol. 1994 Jan;12(1):1-4. doi: 10.1200/JCO.1994.12.1.1. No abstract available.
• Background Klein RD, Van Pelt CS, Sabichi AL, Dela Cerda J, Fischer SM, Furstenberger G, Muller-Decker K. Transitional cell hyperplasia and carcinomas in urinary bladders of transgenic mice with keratin 5 promoter-driven cyclooxygenase-2 overexpression. Cancer Res. 2005 Mar 1;65(5):1808-13. doi: 10.1158/0008-5472.CAN-04-3567.
• Background Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol. 2006 Jun;175(6):2004-10. doi: 10.1016/S0022-5347(06)00264-3.
• Background Malmstrom PU, Wijkstrom H, Lundholm C, Wester K, Busch C, Norlen BJ. 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group. J Urol. 1999 Apr;161(4):1124-7.
• Background Miyata Y, Kanda S, Nomata K, Eguchi J, Kanetake H. Expression of cyclooxygenase-2 and EP4 receptor in transitional cell carcinoma of the upper urinary tract. J Urol. 2005 Jan;173(1):56-60. doi: 10.1097/01.ju.0000148272.77539.2d.
• Background Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G; FAP Study Group. A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut. 2002 Jun;50(6):857-60. doi: 10.1136/gut.50.6.857.
• Background Ristimaki A, Nieminen O, Saukkonen K, Hotakainen K, Nordling S, Haglund C. Expression of cyclooxygenase-2 in human transitional cell carcinoma of the urinary bladder. Am J Pathol. 2001 Mar;158(3):849-53. doi: 10.1016/S0002-9440(10)64033-3.
• Background Serretta V, Pavone C, Ingargiola GB, Daricello G, Allegro R, Pavone-Macaluso M. TUR and adjuvant intravesical chemotherapy in T1G3 bladder tumors: recurrence, progression and survival in 137 selected patients followed up to 20 years. Eur Urol. 2004 Jun;45(6):730-5; discussion 735-6. doi: 10.1016/j.eururo.2003.12.002.
• Background Shariat SF, Kim JH, Ayala GE, Kho K, Wheeler TM, Lerner SP. Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder. J Urol. 2003 Mar;169(3):938-42. doi: 10.1097/01.ju.0000043638.89552.ed.
• Background Shelley MD, Kynaston H, Court J, Wilt TJ, Coles B, Burgon K, Mason MD. A systematic review of intravesical bacillus Calmette-Guerin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer. BJU Int. 2001 Aug;88(3):209-16. doi: 10.1046/j.1464-410x.2001.02306.x.
• Background Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M; Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. doi: 10.1056/NEJMoa050405. Epub 2005 Feb 15.
• Background Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B, Godio L, Patterson S, Rodriguez-Bigas MA, Jester SL, King KL, Schumacher M, Abbruzzese J, DuBois RN, Hittelman WN, Zimmerman S, Sherman JW, Kelloff G. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000 Jun 29;342(26):1946-52. doi: 10.1056/NEJM200006293422603.
• Background Sylvester RJ, van der Meijden AP, Oosterlinck W, Witjes JA, Bouffioux C, Denis L, Newling DW, Kurth K. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006 Mar;49(3):466-5; discussion 475-7. doi: 10.1016/j.eururo.2005.12.031. Epub 2006 Jan 17.
• Background Sylvester RJ, Oosterlinck W, Witjes JA. The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol. 2008 Apr;53(4):709-19. doi: 10.1016/j.eururo.2008.01.015. Epub 2008 Jan 15.
• Background van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, Witjes JA, Zlotta AR. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009 Sep;56(3):430-42. doi: 10.1016/j.eururo.2009.06.028. Epub 2009 Jun 26.
• Background Witjes JA, Hendricksen K. Intravesical pharmacotherapy for non-muscle-invasive bladder cancer: a critical analysis of currently available drugs, treatment schedules, and long-term results. Eur Urol. 2008 Jan;53(1):45-52. doi: 10.1016/j.eururo.2007.08.015. Epub 2007 Aug 20.

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