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Systemic Therapy of Advanced Urothelial Cancer

  • Genitourinary Cancer
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Advanced bladder/urothelial cancer remains an incurable terminal disease, and accounts for 3% of the cancer related mortality in the United States. Systemic chemotherapy achieves palliation, survival benefit, and occasional long-term remissions. The two regimens that have been widely adopted consist of either cisplatin and gemcitabine, or the MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen. Novel therapies are being evaluated in metastatic bladder cancer to improve survival outcomes. A randomized trial of larotaxel (a novel taxane) and cisplatin vs cisplatin and gemcitabine in frontline therapy of metastatic urothelial cancer is ongoing. The studies evaluating therapies targeted frontline involve cisplatin and gemcitabine with or without cetuximab (ongoing), and with or without bevacizumab (CALGB proposed trial). With the advent of adjuvant/neoadjuvant cisplatin-based therapy, and improvement in supportive care, more patients are being considered for second-line therapies in urothelial cancer thus making this a field of emerging importance. The only phase III trial in pretreated urothelial cancer compared vinflunine with best supportive care, and revealed no significant survival improvement. Clinical trials are ongoing with pazopanib, a VEGF inhibitor, and Zactima, a VEGF and EGFR inhibitor. The biggest hurdle to progress in advanced bladder cancer has been the slow accrual to studies in the United States. Making clinical trial participation a␣priority in bladder cancer is the dire need of the moment. At the same time, it is essential to take into account the changing needs of the population afflicted with bladder cancer, and tailor the therapeutic trials to fit a contemporary patient.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jemal A, Siegel R, Ward E, et al.: Cancer statistics, 2008. CA Cancer J Clin 2008, 58:71-96. doi:10.3322/CA.2007.0010.

    Article  PubMed  Google Scholar 

  2. Grossman HB, Natale RB, Tangen CM, et al.: Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003, 349:859–66. doi:10.1056/NEJMoa022148.

    Article  CAS  PubMed  Google Scholar 

A phase III trial revealing significant survival benefit with the use of neoadjuvant chemotherapy in localized bladder cancer.

  1. Cookson MS, Chang SS, Wells N, Parekh DJ, Smith JA Jr: Complications of radical cystectomy for nonmuscle invasive disease: comparison with muscle invasive disease. J Urol. 2003;169:101–104.

    Article  PubMed  Google Scholar 

  2. Herr HW, Schwalb DM, Zhang ZF, et al.: Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial. J Clin Oncol. 1995, 13:1404–1408.

    CAS  PubMed  Google Scholar 

  3. Steinberg, G; Bahnson, R; Brosman, S, et al.: Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guérin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol. 2000, 163:761–767.

    Article  CAS  PubMed  Google Scholar 

  4. Bianco FJ Jr, Justa D, Grignon DJ, et al.: Management of clinical T1 bladder transitional cell carcinoma by radical cystectomy. Urol Oncol. 2004, 4:290–294.

    Google Scholar 

  5. Margulis V, Shariat SF, Matin SF, et al.: Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer 2009 Jan 20 [Epub ahead of print]

  6. Patel B, Forman J, Fontana J, et al.: A single institution experience with concurrent capecitabine and radiation therapy in weak and/or elderly patients with urothelial cancer. Int J Radiat Oncol Biol Phys. 2005, 62:1332–1338.

    Article  CAS  PubMed  Google Scholar 

  7. Walko CM, Lindley C. Capecitabine: A review. Clin Ther. 2005, 27:23–44.

    Article  CAS  PubMed  Google Scholar 

  8. Fabio C. and Sternberg C.N.: Neoadjuvant and adjuvant therapy in muscle invasive bladder cancer. Eur Urol 2009, 55:348–358.

    Article  Google Scholar 

  9. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003, 361: 1927–1934.

    Article  Google Scholar 

  10. Millikan, C. Dinney and D. Swanson et al.: Integrated therapy for locally advanced bladder cancer: Final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol 2001, 19: 4005–4013.

    CAS  PubMed  Google Scholar 

  11. Lara PN, Goldman B, DeVere WR, et al.: A sequential treatment approach to muscle-invasive urothelial cancer: a phase II Southwest Oncology Group Trial (S0219) of neoadjuvant paclitaxel, carboplatin, and gemcitabine (PCG). J Clin Oncol 2008, 26 (abstract # 5022)

  12. Smith DC, Mackler NJ, Dunn RL, et al. Phase II trial of paclitaxel, carboplatin and gemcitabine in patients with locally advanced carcinoma of the bladder. J Urol. 2008, 180:2384–2388.

    Article  CAS  PubMed  Google Scholar 

  13. Sternberg CN, Yagoda A, Scher HI, et al.: M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium. J Urol. 1988, 139:461–469.

    CAS  PubMed  Google Scholar 

  14. Saxman SB, Propert KJ, Einhorn LH, et al.: Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study. J Clin Oncol 1997, 15:2564–2569.

    CAS  PubMed  Google Scholar 

  15. H. von derMaase, S.W. Hansen, J.T. Roberts, et al.: Gemcitabine 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 2000, 18:3068–3077.

    PubMed  Google Scholar 

A randomized trial proving the non inferiority of cisplatin and gemcitabine as compared to MVAC with less toxicity hence establishing a new standard in metastatic urothelial cancer.

  1. Redman BG, Smith DC, Flaherty L, et al.: Phase II trial of paclitaxel and carboplatin in the treatment of advanced urothelial carcinoma. J Clin Oncol. 1998, 16:1844–1888.

    CAS  PubMed  Google Scholar 

  2. M. Hussain, U. Vaishampayan, W. Du, et al.: Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer, J Clin Oncol 2001, 19: 2527–2533.

    CAS  PubMed  Google Scholar 

  3. J.D. Hainsworth, A.A. Meluch, S. Litchy, et al.: Paclitaxel, carboplatin, and gemcitabine in the treatment of patients with advanced transitional cell carcinoma of the urothelium, Cancer 2005, 103: 2298–2303.

    Article  CAS  PubMed  Google Scholar 

  4. Bellmunt J, von der Maase H, Mead GM, et al.: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study. ASCO 2007 (abstract # LBA5030)

  5. Bajorin DF, Dodd PM, Mazumdar M, et al.: Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999, 17:3173–3181.

    CAS  PubMed  Google Scholar 

  6. De Wit R.: European Organization for Research and Treatment. Overview of bladder cancer trials in the European Organization for Research and Treatment. Cancer. 2003, 97(8 Suppl):2120–2126.

    Article  PubMed  Google Scholar 

  7. Witte RS, Elson P, Bono B, et al.: Eastern Cooperative Oncology Group trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol 15:589–593, 1997.

    CAS  PubMed  Google Scholar 

  8. Kim J, Millikan RE, SmithTL, et al.: Treating refractory advanced or metastatic urothelial carcinoma with interleukin-2: a phase II study. Urol Oncol 2003, 21:21–26.

    CAS  PubMed  Google Scholar 

  9. Witte RS, Elson P, Khandakar J, et al.: An Eastern Oncology Group phase II trial of trimetrexate in the treatment of advanced urothelial carcinoma. Cancer 1994, 73:688–691.

    Article  CAS  PubMed  Google Scholar 

  10. C. Sweeney, Roth BJ, Kabbinavar FF, et al.: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the bladder. J Clin Oncol 2006, 24:3451–3457.

    Article  CAS  PubMed  Google Scholar 

  11. Vaishampayan UN, Faulkner JR, Small EJ, et al.: Phase II trial of carboplatin and paclitaxel in cisplatin-pretreated advanced transitional cell carcinoma: a Southwest Oncology Group study. Cancer. 2005 Oct 15;104(8):1627–32.

    Article  CAS  PubMed  Google Scholar 

  12. Uhm JE, Lim HY, Kim WS, et al.: Paclitaxel with cisplatin as salvage treatment for patients with previously treated advanced transitional cell carcinoma of the urothelial tract. Neoplasia. 2007, 1:18–22.

    Article  Google Scholar 

  13. Carles J, Esteban E, Climent M, et al.: Gemcitabine and oxaliplatin combination: a multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer. Ann Oncol. 2007, 8:1359–1362.

    Article  Google Scholar 

  14. Logothetis CJ, Dexeus FH, Sella A, et al.: Escalated therapy for refractory urothelial tumors; methotrexate-vinblastine-doxorubicin-cisplatin plus unglycosylated recombinant human granulocyte-macrophage colony- stimulating factor. J Natl Cancer Inst 1990, 18:667–672.

    Article  Google Scholar 

  15. Culine S, Theodore C, De Santis M, et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006, 94:1395–1401.

    Article  CAS  PubMed  Google Scholar 

  16. Bellmunt Molins J, von der Maase H, Theodore C, et al.: Randomised phase III trial of vinflunine (V) plus best supportive care (B) vs B alone as 2nd line therapy after a platinum-containing regimen in advanced transitional cell carcinoma of the urothelium (TCCU). J Clin Oncol 2008, 26 (abstr 5028)

  17. Jimenez RE, Hussain M, Bianco FJ Jr, et al.:Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin Cancer Res. 2001, 8:2440–2447.

    Google Scholar 

  18. M.H. Hussain, G.R. MacVicar, D.P. Petrylak, et al.: Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial, J Clin Oncol 2007, 25: 2218–2224.

    Article  CAS  PubMed  Google Scholar 

  19. Bradley DA, Dunn R, Nanus D, et al.: Randomized, double-blind, placebo-controlled phase II trial of maintenance sunitinib versus placebo after chemotherapy for patients with advanced urothelial carcinoma: scientific rationale and study design. Clin Genitourin Cancer 2007, 5:460–463.

    Article  CAS  PubMed  Google Scholar 

  20. Sakr W, Marur S, Che M, et al.: Expression of EGFR, HER-2 and p53 predictive of prognosis in muscle-invasive bladder cancer. ASCO 2007 (abstract # 15637)

  21. Bellmunt J, Hussain M, Dinney CP.: Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. Crit Rev Oncol Hematol. 2003, 46 Suppl:S85-104.

    Article  Google Scholar 

  22. Philips GK, Halabi S, Sanford BL, et al.: A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102. Ann Oncol 2009 Jan 23 [Epub ahead of print]

  23. McHugh LA, Kriajevska M, Mellon JK, Griffiths TR.: Combined treatment of bladder cancer cell lines with lapatinib and varying chemotherapy regimens—evidence of schedule-dependent synergy. Urology. 2007,69:390–394.

    Article  PubMed  Google Scholar 

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  1. 4HWCRC, 4100 John R, Detroit, MI, 48201, USA

    Ulka Vaishampayan MD

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  1. Ulka Vaishampayan MD
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Vaishampayan, U. Systemic Therapy of Advanced Urothelial Cancer. Curr. Treat. Options in Oncol. 10, 256–266 (2009). https://doi.org/10.1007/s11864-009-0101-9

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