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Beyond BCG: Gemcitabine

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Bladder Cancer

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

Currently, recurrence of carcinoma in situ (CIS) after intravesical BCG mandates a radical cystectomy, as BCG-refractory CIS is aggressive with a high propensity for progression. Novel intravesical agents are needed to salvage refractory disease. Gemcitabine is an antimetabolite with proven single agent efficacy against metastatic bladder cancer. In this review, the ability of gemcitabine to treat BCG-refractory CIS is examined in preclinical, phase I and phase II trials. Future studies with intravesical gemcitabine are also examined.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, and Thun MJ. Cancer statistics, 2006. CA Cancer J Clin 56: 106–30, 2006.

    Article  PubMed  Google Scholar 

  2. Herr HW. Tumor progression and survival of patients with high grade, noninvasive papillary (TaG3) bladder tumors: 15-year outcome. J Urol 163: 60–1; discussion 61–2, 2000.

    Article  CAS  PubMed  Google Scholar 

  3. Herr HW. Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. J Clin Oncol 19: 89–93, 2001.

    CAS  PubMed  Google Scholar 

  4. Morales A, Eidinger D, and Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 167: 891–3; discussion 893–5, 2002.

    Article  CAS  PubMed  Google Scholar 

  5. Shelley MD, Court JB, Kynaston H, Wilt TJ, Coles B, and Mason M. Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev CD003231, 2003.

    Google Scholar 

  6. Herr HW, Wartinger DD, Fair WR, and Oettgen HF. Bacillus Calmette-Guerin therapy for superficial bladder cancer: a 10-year followup. J Urol 147: 1020–3, 1992.

    CAS  PubMed  Google Scholar 

  7. Herr HW, Badalament RA, Amato DA, Laudone VP, Fair WR, and Whitmore WF, Jr. Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression. J Urol 141: 22–9, 1989.

    CAS  PubMed  Google Scholar 

  8. Herr HW 2005 Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. J Urol 174: 2134–7.

    Article  PubMed  Google Scholar 

  9. Dalbagni G, Rechtschaffen T, and Herr HW. Is transurethral biopsy of the bladder necessary after 3 months to evaluate response to bacillus Calmette-Guerin therapy? J Urol 162: 708–9, 1999.

    Article  CAS  PubMed  Google Scholar 

  10. Cookson MS, Herr HW, Zhang ZF, Soloway S, Sogani PC, and Fair WR. The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 158: 62–7, 1997.

    Article  CAS  PubMed  Google Scholar 

  11. Herr HW and Dalbagni G. Defining bacillus Calmette-Guerin refractory superficial bladder tumors. J Urol 169: 1706–8, 2003.

    Article  CAS  PubMed  Google Scholar 

  12. Mini E, Nobili S, Caciagli B, Landini I, and Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol 17 Suppl 5: v7–v12, 2006.

    Article  PubMed  Google Scholar 

  13. Hui YF and Reitz J. Gemcitabine: a cytidine analogue active against solid tumors. Am J Health Syst Pharm 54: 162–70; quiz 197–8, 1997.

    CAS  PubMed  Google Scholar 

  14. Plunkett W, Huang P, and Gandhi V. Preclinical characteristics of gemcitabine. Anticancer Drugs 6 Suppl 6: 7–13, 1995.

    Article  CAS  PubMed  Google Scholar 

  15. Plunkett W, Huang P, Searcy CE, and Gandhi V. Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol 23: 3–15, 1996.

    CAS  PubMed  Google Scholar 

  16. Storniolo AM, Allerheiligen SR, and Pearce HL. Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol 24: S7-2–S7-7, 1997.

    CAS  PubMed  Google Scholar 

  17. Michael M and Moore M. Clinical experience with gemcitabine in pancreatic carcinoma. Oncology (Williston Park) 11: 1615–22; discussion 1622, 1625–7, 1997.

    Google Scholar 

  18. Heinemann V. Gemcitabine in metastatic breast cancer. Expert Rev Anticancer Ther 5: 429–43, 2005.

    Article  CAS  PubMed  Google Scholar 

  19. Bookman MA. Gemcitabine monotherapy in recurrent ovarian cancer: from the bench to the clinic. Int J Gynecol Cancer 15 Suppl 1: 12–7, 2005.

    Article  PubMed  Google Scholar 

  20. Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, and Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol 22: 3–10, 1995.

    CAS  PubMed  Google Scholar 

  21. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Eur Urol 48: 189–199; discussion 199–201, 2005.

    Article  Google Scholar 

  22. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev CD005246, 2005.

    Google Scholar 

  23. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM et al, 2000Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18: 3068–77.

    CAS  PubMed  Google Scholar 

  24. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, and Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23: 4602–8, 2005.

    Article  CAS  PubMed  Google Scholar 

  25. von der Maase H. Current and future perspectives in advanced bladder cancer: is there a new standard? Semin Oncol 29: 3–14, 2002.

    Article  PubMed  Google Scholar 

  26. Kilani RT, Tamimi Y, Karmali S, Mackey J, Hanel EG, Wong KK, and Moore RB. Selective cytotoxicity of gemcitabine in bladder cancer cell lines. Anticancer Drugs 13: 557–66, 2002.

    Article  CAS  PubMed  Google Scholar 

  27. Cozzi PJ, Bajorin DF, Tong W, Nguyen H, Scott J, Heston WD, and Dalbagni G. Toxicology and pharmacokinetics of intravesical gemcitabine: a preclinical study in dogs. Clin Cancer Res 5: 2629–37, 1999.

    CAS  PubMed  Google Scholar 

  28. Matera M, Costantino G, Clementi G, Lempereur L, Vasta D, and Vasquez E. Experimental study on the toxicity and the local and systemic tolerability of gemcitabine after topical treatment of the rabbit bladder. Oncol Rep 11: 1145–51, 2004.

    CAS  PubMed  Google Scholar 

  29. Witjes JA, Vriesema JL, van der Heijden AG, Peters GJ, and Schalken JA. Pharmacokinetics of intravesical gemcitabine: a preclinical study in pigs. Eur Urol 44: 615–9, 2003.

    Article  CAS  PubMed  Google Scholar 

  30. Dalbagni G, Russo P, Sheinfeld J, Mazumdar M, Tong W, Rabbani F, Donat MS, Herr HW, Sogani P, dePalma D et al, 2002. Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder. J Clin Oncol 20: 3193–8.

    Article  CAS  PubMed  Google Scholar 

  31. Laufer M, Ramalingam S, Schoenberg MP, Haisfield-Wolf ME, Zuhowski EG, Trueheart IN, Eisenberger MA, Nativ O, and Egorin MJ. Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: a phase I and pharmacokinetic study. J Clin Oncol 21: 697–703, 2003.

    Article  CAS  PubMed  Google Scholar 

  32. Witjes JA, van der Heijden AG, Vriesema JL, Peters GJ, Laan A, and Schalken JA. Intravesical gemcitabine: a phase 1 and pharmacokinetic study. Eur Urol 45: 182–6, 2004.

    Article  CAS  PubMed  Google Scholar 

  33. De Berardinis E, Antonini G, Peters GJ, Loves WJ, Van der Born K, Codacci-Pisanelli G, and Di Silverio F. Intravesical administration of gemcitabine in superficial bladder cancer: a phase I study with pharmacodynamic evaluation. BJU Int 93: 491–4, 2004.

    Article  CAS  PubMed  Google Scholar 

  34. Palou J, Carcas A, Segarra J, Duque B, Salvador J, Garcia-Ribas I, and Villavicencio H. Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer. J Urol 172: 485–8, 2004.

    Article  CAS  PubMed  Google Scholar 

  35. Campodonico F and Maffezzini M. Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of the bladder. Urology 66: 1141–2; author reply 1142, 2005.

    Article  PubMed  Google Scholar 

  36. Bassi P, De Marco V, Tavolini IM, Longo F, Pinto F, Zucchetti M, Crucitta E, Marini L, and Dal Moro F. Pharmacokinetic study of intravesical gemcitabine in carcinoma in situ of the bladder refractory to bacillus Calmette-Guerin therapy. Urol Int 75: 309–13, 2005.

    Article  CAS  PubMed  Google Scholar 

  37. Mattioli F, Curotto A, Manfredi V, Gosmar M, Garbero C, Ambruosi C, Carmignani G, and Martelli A. Intravesical gemcitabine in superficial bladder cancer: a phase II safety, efficacy and pharmacokinetic study. Anticancer Res 25: 2493–6, 2005.

    CAS  PubMed  Google Scholar 

  38. Gontero P and Frea B. Actual experience and future development of gemcitabine in superficial bladder cancer. Ann Oncol 17 Suppl 5: v123–8, 2006.

    Article  PubMed  Google Scholar 

  39. Gontero P, Casetta G, Maso G, Sogni F, Pretti G, Zitella A, Frea B, and Tizzani A. Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC). Eur Urol 46: 339–43, 2004.

    Article  CAS  PubMed  Google Scholar 

  40. Serretta V, Galuffo A, Pavone C, Allegro R, and Pavone-MacAluso M. Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of bladder: Phase I-II study on marker lesions. Urology 65: 65–9, 2005.

    Article  PubMed  Google Scholar 

  41. Dalbagni G, Russo P, Bochner B, Ben-Porat L, Sheinfeld J, Sogani P, Donat MS, Herr HW, and Bajorin D. Phase II trial of intravesical gemcitabine in bacille Calmette-Guerin-refractory transitional cell carcinoma of the bladder. J Clin Oncol 24: 2729–34, 2006.

    Article  CAS  PubMed  Google Scholar 

  42. Bartoletti R, Cai T, Gacci M, Giubilei G, Viggiani F, Santelli G, Repetti F, Nerozzi S, Ghezzi P, and Sisani M. Intravesical gemcitabine therapy for superficial transitional cell carcinoma: results of a Phase II prospective multicenter study. Urology 66: 726–31, 2005.

    Article  PubMed  Google Scholar 

  43. Gardmark T, Carringer M, Beckman E, and Malmstrom PU. Randomized phase II marker lesion study evaluating effect of scheduling on response to intravesical gemcitabine in recurrent Stage Ta urothelial cell carcinoma of the bladder. Urology 66: 527–30, 2005.

    Article  PubMed  Google Scholar 

  44. Gontero P, Marini L, and Frea B. Intravesical gemcitabine for superficial bladder cancer: rationale for a new treatment option. BJU Int 96: 970–6, 2005.

    Article  CAS  PubMed  Google Scholar 

  45. Brocks CP, Buttner H, and Bohle A. Inhibition of tumor implantation by intravesical gemcitabine in a murine model of superficial bladder cancer. J Urol 174: 1115–8, 2005.

    Article  PubMed  Google Scholar 

  46. Huncharek M and Kupelnick B. Impact of intravesical chemotherapy versus BCG immunotherapy on recurrence of superficial transitional cell carcinoma of the bladder: metaanalytic reevaluation. Am J Clin Oncol 26: 402–7, 2003.

    Article  CAS  PubMed  Google Scholar 

  47. Miyake H, Eto H, Hara I, So A, Li D, and Gleave ME. Synergistic antitumor activity by combined treatment with gemcitabine and antisense oligodeoxynucleotide targeting clusterin gene in an intravesical administration model against human bladder cancer kotcc-1 cells. J Urol 171: 2477–81, 2004.

    Article  CAS  PubMed  Google Scholar 

  48. Perabo FG, Lindner H, Schmidt D, Huebner D, Blatter J, Fimmers R, Muller SC, and Albers P. Preclinical evaluation of gemcitabine/paclitaxel-interactions in human bladder cancer lines. Anticancer Res 23: 4805–14, 2003.

    CAS  PubMed  Google Scholar 

  49. Perabo FG and Muller SC. New agents in intravesical chemotherapy of superficial bladder cancer. Scand J Urol Nephrol 39: 108–16, 2005.

    Article  CAS  PubMed  Google Scholar 

  50. Zoli W, Ricotti L, Tesei A, Ulivi P, Gasperi Campani A, Fabbri F, Gunelli R, Frassineti GL, and Amadori D. Schedule-dependent cytotoxic interaction between epidoxorubicin and gemcitabine in human bladder cancer cells in vitro. Clin Cancer Res 10: 1500–7, 2004.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Ganesh V. Raj & Guido Dalbagni

Authors
  1. Ganesh V. Raj
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  2. Guido Dalbagni
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Correspondence to Guido Dalbagni .

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Editors and Affiliations

  1. Dept. Urology, University of Michigan Health System, E. Medical Center Dr. 1500 , Ann Arbor, 48109-0252, U.S.A.

    Cheryl T. Lee

  2. Dept. Urology, University of Michigan Health System, E. Medical Center Dr. 1500 , Ann Arbor, 48109-0252, U.S.A.

    David P. Wood

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Raj, G.V., Dalbagni, G. (2009). Beyond BCG: Gemcitabine. In: Lee, C., Wood, D. (eds) Bladder Cancer. Current Clinical Urology. Humana Press. https://doi.org/10.1007/978-1-59745-417-9_12

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  • DOI: https://doi.org/10.1007/978-1-59745-417-9_12

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-988-8

  • Online ISBN: 978-1-59745-417-9

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