Subscribe to RSS
DOI: 10.1055/s-0032-1327699
Chemotherapie des Urothelkarzinoms der Harnblase – Update 2012
Chemotherapy for Urothelial Cancer of the Bladder – Update 2012Publication History
Publication Date:
29 November 2012 (online)
![](https://www.thieme-connect.de/media/uro/201206/lookinside/thumbnails/10.1055-s-0032-1327699-1.jpg)
Zusammenfassung
Etwa die Hälfte der Patienten mit einem muskelinvasiven Urothelkarzinom der Harnblase weist trotz radikaler Zystektomie mit pelviner Lymphadenektomie im weiteren Verlauf ein Rezidiv auf. Durch den Einsatz einer neoadjuvanten Chemotherapie wird das tumorspezifische und das Gesamtüberleben der Patienten verbessert, auch wenn es bislang noch nicht möglich ist, zu definieren, welcher Patient tatsächlich von einem neoadjuvanten Therapieregime profitiert und welcher nicht. Die Wirksamkeit einer adjuvanten Behandlung ist hingegen bislang nicht belegt. Beim metastasierten Urothelkarzinom der Harnblase ist eine Chemotherapie in der Regel eine palliative Therapieoption. Dennoch kann bei einem signifikanten Anteil der Patienten eine adäquate Stabilisierung des Krankheitsprogress ggf. auch mit einem Langzeitansprechen erreicht werden. Wichtige Entscheidungshilfen für die Indikation zur Chemotherapie sind dabei kürzlich identifizierte klinische Prognosefaktoren. Diese Arbeit gibt einen Überblick über die aktuellen Standards und Entwicklungen in der Chemotherapie des Urothelkarzinoms der Harnblase und soll eine Grundlage für eine sinnvolle Therapieentscheidung im klinischen Alltag sein.
Abstract
Despite adequate surgical treatment by radical cystectomy and pelvic lymphadenectomy, about half of patients suffering from muscle-invasive urothelial bladder cancer will die. Both overall and cancer-specific survival has been improved by neoadjuvant chemotherapy. However, it is still not possible to predict who is likely to benefit from neoadjuvant treatment and who will not. In contrast to neoadjuvant chemotherapy, the efficacy of adjuvant chemotherapy has not definitely been proven. In metastatic urothelial cancer chemotherapy is usually a palliative treatment option. However, in a significant proportion of patients, disease stabilisation and even long-term response can be achieved. Important advances to tailor first- and second-line chemotherapy have recently been reported for clinical prognostic parameters. This review discusses the current standards and developments in the chemotherapeutic treatment of urothelial bladder cancer. Furthermore, it should provide a framework for reasonable treatment choices in daily clinical practice.
-
Literatur
- 1 Robert-Koch-Institut. Daten zur Krebsinzidenz und -mortalität in Deutschland. In Krebs in Deutschland 2010 www.rki.de
- 2 Sylvester RJ, van der Meijden AP, Oosterlinck W et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2 596 patients from seven EORTC trials. Eur Urol 2006; 49: 465-466 discussion 467–475
- 3 Kiemeney LA, Witjes JA, Verbeek AL et al. The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. Br J Cancer 1993; 67: 806-812
- 4 Rogers CG, Palapattu GS, Shariat SF et al. Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder. J Urol 2006; 175: 2048-2053 discussion 2053
- 5 Hautmann RE, Gschwend JE, de Petriconi RC et al. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006; 176: 486-492 discussion 482-491
- 6 Madersbacher S, Hochreiter W, Burkhard F et al. Radical cystectomy for bladder cancer today – a homogeneous series without neoadjuvant therapy. J Clin Oncol 2003; 21: 690-696
- 7 von der Maase H, Sengelov L, Roberts JT et al. 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 2005; 23: 4602-4608
- 8 Winquist E, Kirchner TS, Segal R et al. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004; 171: 561-569
- 9 ABC-Meta-analysis-Collaboration . Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005; 48: 202-205 discussion 205-206
- 10 ABC-Meta-analysis-Collaboration . Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003; 361: 1927-1934
- 11 Sherif A, Rintala E, Mestad O et al. Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer – Nordic cystectomy trial 2. Scand J Urol Nephrol 2002; 36: 419-425
- 12 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: 859-866
- 13 Malmstrom PU, Rintala E, Wahlqvist R et al. Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group. J Urol 1996; 155: 1903-1906
- 14 Inernational-Collaboration-of-Trialists . Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet 1999; 354: 533-540
- 15 Griffiths G, Hall R, Sylvester R et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 2011; 29: 2171-2177
- 16 Sternberg CN, de Mulder PH, Schornagel JH et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol 2001; 19: 2638-2646
- 17 von der Maase H, Hansen SW, Roberts JT 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
- 18 Canter D, Viterbo R, Kutikov A et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 2011; 77: 160-165
- 19 Raj GV, Karavadia S, Schlomer B et al. Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer. Cancer 2011; 117: 276-282
- 20 Scosyrev E, Messing EM, van Wijngaarden E et al. Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder. Cancer 2012; 118: 72-81
- 21 Yeshchina O, Badalato GM, Wosnitzer MS et al. Relative efficacy of perioperative gemcitabine and Cisplatin versus methotrexate, vinblastine, adriamycin, and Cisplatin in the management of locally advanced urothelial carcinoma of the bladder. Urology 2012; 79: 384-390
- 22 Dash A, JAt Pettus, Herr HW et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 2008; 113: 2471-2477
- 23 Koga F, Kihara K, Fujii Y et al. Favourable outcomes of patients with clinical stage T3N0M0 bladder cancer treated with induction low-dose chemo-radiotherapy plus partial or radical cystectomy vs immediate radical cystectomy: a single-institutional retrospective comparative study. BJU Int 2009; 104: 189-194
- 24 Svatek RS, Shariat SF, Novara G et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort. BJU Int 2011;
- 25 Rajesh A, Sokhi HK, Fung R et al. Bladder cancer: evaluation of staging accuracy using dynamic MRI. Clin Radiol 2011; 66: 1140-1145
- 26 Tekes A, Kamel I, Imam K et al. Dynamic MRI of bladder cancer: evaluation of staging accuracy. AJR Am J Roentgenol 2005; 184: 121-127
- 27 Baltaci S, Resorlu B, Yagci C et al. Computerized tomography for detecting perivesical infiltration and lymph node metastasis in invasive bladder carcinoma. Urol Int 2008; 81: 399-402
- 28 Lodde M, Lacombe L, Friede J et al. Evaluation of fluorodeoxyglucose positron-emission tomography with computed tomography for staging of urothelial carcinoma. BJU Int 2010; 106: 658-663
- 29 Picchio M, Treiber U, Beer AJ et al. Value of 11C-choline PET and contrast-enhanced CT for staging of bladder cancer: correlation with histopathologic findings. J Nucl Med 2006; 47: 938-944
- 30 Saokar A, Islam T, Jantsch M et al. Detection of lymph nodes in pelvic malignancies with Computed Tomography and Magnetic Resonance Imaging. Clin Imaging 2010; 34: 361-366
- 31 Apolo AB, Riches J, Schoder H et al. Clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in bladder cancer. J Clin Oncol 2010; 28: 3973-3978
- 32 Swinnen G, Maes A, Pottel H et al. FDG-PET/CT for the preoperative lymph node staging of invasive bladder cancer. Eur Urol 2010; 57: 641-647
- 33 Smith SC, Baras AS, Dancik G et al. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol 2011; 12: 137-143
- 34 [Anonym] . 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 2005; 48: 189-199 discussion 199–201
- 35 Wiesner C, Salzer A, Thomas C et al. Cancer-specific survival after radical cystectomy and standardized extended lymphadenectomy for node-positive bladder cancer: prediction by lymph node positivity and density. BJU Int 2009; 104: 331-335
- 36 Bruins HM, Huang GJ, Cai J et al. Clinical outcomes and recurrence predictors of lymph node positive urothelial cancer after cystectomy. J Urol 2009; 182: 2182-2187
- 37 Lehmann J, Retz M, Wiemers C et al. Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95). J Clin Oncol 2005; 23: 4963-4974
- 38 Paz-Ares LG, Solsona E, Esteban E et al. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. Chicago: ASCO; 2010
- 39 Cognetti F, Ruggeri EM, Felici A et al. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol 2012; 23: 695-700
- 40 Svatek RS, Shariat SF, Lasky RE et al. The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clin Cancer Res 2010; 16: 4461-4467
- 41 Stadler WM, Lerner SP, Groshen S et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011; 29: 3443-3449
- 42 Ghoneim MA, Abdel-Latif M, el-Mekresh M et al. Radical cystectomy for carcinoma of the bladder: 2 720 consecutive cases 5 years later. J Urol 2008; 180: 121-127
- 43 Kassouf W, Svatek RS, Shariat SF et al. Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. Urol Oncol 2011;
- 44 Lehmann J, Suttmann H, Albers P et al. Surgery for metastatic urothelial carcinoma with curative intent: the German experience (AUO AB 30/05). Eur Urol 2009; 55: 1293-1299
- 45 Roberts JT, von der Maase H, Sengelov L et al. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer. Ann Oncol 2006; 17 (Suppl. 05) v118-v122
- 46 Bellmunt J, von der Maase H, Mead GM et al. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol 2012;
- 47 Hahn NM, Stadler WM, Zon RT et al. Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04-75. J Clin Oncol 2011; 29: 1525-1530
- 48 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; 20: 1074-1079
- 49 Hussain MH, MacVicar GR, Petrylak DP 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
- 50 Krege S, Rexer H, vom Dorp F et al. Gemcitabine and cisplatin with or without sorafenib in urothelial carcinoma (AUO-AB 31/05). Chicago: ASCO; 2010
- 51 Galsky MD, Sonpavde G, Hellerstedt BA et al. Phase II study of gemcitabine, cisplatin, and sunitinib in patients with advanced urothelial carcinoma (UC). Chicago: ASCO; 2010
- 52 Sridhar SS, Winquist E, Eisen A et al. A phase II trial of sorafenib in first-line metastatic urothelial cancer: a study of the PMH Phase II Consortium. Invest New Drugs 2011; 29: 1045-1049
- 53 Bellmunt J, Theodore C, Demkov T et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27: 4454-4461
- 54 Sweeney CJ, Williams SD, Finch DE et al. A Phase II study of paclitaxel and ifosfamide for patients with advanced refractory carcinoma of the urothelium. Cancer 1999; 86: 514-518
- 55 Soga N, Onishi T, Arima K et al. Paclitaxel Carboplatin chemotherapy as a second-line chemotherapy for advanced platinum resistant urothelial cancer in Japanese cases. Int J Urol 2007; 14: 828-832
- 56 Lin CC, Hsu CH, Huang CY et al. Gemcitabine and ifosfamide as a second-line treatment for cisplatin-refractory metastatic urothelial carcinoma: a phase II study. Anticancer Drugs 2007; 18: 487-491
- 57 Krege S, Rembrink V, Borgermann C et al. Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study. J Urol 2001; 165: 67-71
- 58 Albers P, Park SI, Niegisch G et al. Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]. Ann Oncol 2011; 22: 288-294
- 59 Sternberg CN, Calabro F, Pizzocaro G et al. Chemotherapy with an every-2-week regimen of gemcitabine and paclitaxel in patients with transitional cell carcinoma who have received prior cisplatin-based therapy. Cancer 2001; 92: 2993-2998
- 60 Fechner G, Siener R, Reimann M et al. Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99). Int J Clin Pract 2006; 60: 27-31
- 61 Kanai K, Kikuchi E, Ohigashi T et al. Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy. Int J Clin Oncol 2008; 13: 510-514
- 62 Suyama T, Ueda T, Fukasawa S et al. Combination of gemcitabine and paclitaxel as second-line chemotherapy for advanced urothelial carcinoma. Jpn J Clin Oncol 2009; 39: 244-250
- 63 Wulfing C, Machiels JP, Richel DJ et al. A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer 2009; 115: 2881-2890
- 64 Petrylak DP, Tangen CM, Van Veldhuizen Jr PJ et al. Results of the Southwest Oncology Group phase II evaluation (study S0031) of ZD1839 for advanced transitional cell carcinoma of the urothelium. BJU Int 2010; 105: 317-321
- 65 Dreicer R, Li H, Stein M et al. Phase 2 trial of sorafenib in patients with advanced urothelial cancer: a trial of the Eastern Cooperative Oncology Group. Cancer 2009; 115: 4090-4095
- 66 Gallagher DJ, Milowsky MI, Gerst SR et al. Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 2010; 28: 1373-1379
- 67 Necchi A, Nicolai N, Ortega C et al. Updated results of INT70/09 phase II study of pazopanib (PZP) monotherapy for patients with relapsed/refractory urothelial cancer (UC). Chicago: ASCO; 2012
- 68 Milowsky MI, Regazzi AM, Garcia-Grossman IR et al. Final results of a phase II study of everolimus (RAD001) in metastatic transitional cell carcinoma (TCC) of the urothelium. Chicago: ASCO; 2011
- 69 Seront E, Rottey S, Sautois B et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Ann Oncol 2012;
- 70 Niegisch G, Retz M, Thalgott MK et al. Second-line treatment of advanced urothelial cancer with paclitaxel and RAD001 (everolimus) in a German phase II trial (AUO trial AB 35/09). Chicago: ASCO; 2012
- 71 Wong YN, Litwin S, Vaughn D et al. Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma. J Clin Oncol 2012;
- 72 Dash A, Galsky MD, Vickers AJ et al. Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer 2006; 107: 506-513
- 73 Balducci L, Yates J. General guidelines for the management of older patients with cancer. Oncology (Williston Park) 2000; 14: 221-227
- 74 De Santis M, Bellmunt J, Mead G et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012; 30: 191-199
- 75 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
- 76 Bellmunt J, Albanell J, Paz-Ares L et al. Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer 2002; 95: 751-757
- 77 Bellmunt J, Choueiri TK, Fougeray R et al. Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol 2010; 28: 1850-1855
- 78 Niegisch G, Fimmers R, Siener R et al. Prognostic Factors in Second-Line Treatment of Urothelial Cancers With Gemcitabine and Paclitaxel (German Association of Urological Oncology Trial AB20/99). Eur Urol 2011; 60: 1087-1096
- 79 Bellmunt J, Paz-Ares L, Cuello M et al. Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol 2007; 18: 522-528
- 80 Als AB, Dyrskjot L, von der Maase H et al. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer. Clin Cancer Res 2007; 13: 4407-4414
- 81 Gallagher D, Joseph V, Garcia-Grossman IR et al. Germline single-nucleotide polymorphisms (SNPs) associated with response of urothelial carcinoma (UC) to platinum-based therapy: The role of the host. Chicago: ASCO; 2011