Transitional cell carcinoma of the urothelial tract is the second most common cancer of the genitourinary system and the fifth most common cancer in Western countries with more than 300,000 new cases per year worldwide. Following the introduction of cisplatin-based chemotherapy, median overall survival in patients with metastatic disease has doubled, demonstrating chemotherapy as an important treatment modality in advanced or metastatic disease. Patients ‘unfit’ to receive cisplatin-based chemotherapy are characterized by impaired renal function, impaired performance status, and/or comorbidity that preclude the use of cisplatin. In this review we summarize the different chemotherapeutic schemes, focusing on treatment options in cisplatin ‘unfit’ patients.
Ardavanis, A., Tryfonopoulos, D., Alexopoulos, A., Kandylis, C., Lainakis, G. and Rigatos, G. ( 2005) Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. Br J Cancer92: 645-650.
2.
Bajorin, D.F., Dodd, P.M., Mazumdar, M., Fazzari, M., McCaffrey, J.A., Scher, H.I. et al. (1999) Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol17: 3173-3181.
3.
Bamias, A., Tiliakos, I., Karali, M.-D. and Dimopoulos, A. ( 2006) Systemic chemotherapy in inoperable or metastatic bladder cancer. Ann Oncol17: 553-561.
4.
Bellmunt, J., de Wit, R., Albanell, J. and Baselga, J. ( 2001) A feasibility study of carboplatin with fixed dose of gemcitabine in ‘unfit’ patients with advanced bladder cancer. Eur J Cancer 37: 2212-2215.
5.
Bellmunt, J., Ribas, A., Eres, N., Albanell, J., Almanza, C., Bermejo, B. et al. (1997) Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma. Cancer80: 1966-1972.
6.
Calabro, F., Lorusso, V., Rosati, G., Manzione, L., Frassineti, L., Sava, T. et al. (2009) Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma. Cancer115: 2652-2659.
7.
Connor, J.P., Olsson, C.A., Benson, M.C., Rapoport, F. and Sawczuk, I.S. ( 1989) Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of the urinary bladder: cause for concern. Urology34: 353-356.
8.
Dash, A., Galsky, M.D., Vickers, A.J., Serio, A.M., Koppie, T.M., Dalbagni, G. et al. (2006) Impact of renal impairment of eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer107: 506-513.
9.
de Santis, M., Bellmunt, J., Mead, G., Kerst, M., Leahy, M., Maroto, P. et al. (2009) Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer ‘unfit’ for cisplatin-based chemotherapy: phase II - results of EORTC study 30986. J Clin Oncol27: 5634-5639.
10.
de Wit, R.(2003) Overview of bladder cancer trials in the European Organization for Research and Treatment. Cancer97: 2120-2126.
11.
de Wit, R. and Bellmunt, J.(2003) Overview of gemcitabine triplets in metastatic bladder cancer. Crit Rev Oncol Hemat45: 191-197.
12.
Dogliotti, L., Carteni, G., Siena, S., Bertetto, O., Martoni, A., Bono, A. et al. (2007) Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol52: 134-141.
13.
Dreicer, R., Li, H., Cooney, M.M., Wilding, G. and Roth, B.J. ( 2008) Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802). Cancer112: 2671-2675.
14.
Dumez, H., Martens, M., Selleslach, J., Guetens, G., De Boeck, G., Aerts, R. et al. (2007) Docetaxel and gemcitabine combination therapy in advanced transitional cell carcinoma of the urothelium: results of a phase II and pharmacologic study. Anti-Cancer Drugs18: 211-218.
15.
Gitlitz, B.J., Baker, C., Chapman, Y., Allen, H.J., Bosserman, L.D., Patel, R. et al. (2003) A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma. Cancer98: 1863-1869.
16.
Iaffaioli, R.V., Tortoriello, A., Facchini, G., Caponigro, F., Gentile, M., Marzano, N. et al. (1999) Phase I-II study of gemcitabine and carboplatin in stage IIIB-IV non-small-cell lung cancer. J Clin Oncol17: 921-926.
17.
Kouno, T., Ando, M., Yonemori, K., Matsumoto, K., Shimizu, C., Katsumata, N. et al. (2007) Weekly paclitaxel and carboplatin against advanced transitional cell cancer after failure of a platinum-based regimen. Eur Urol52: 1115-1122.
18.
Li, J., Juliar, B., Yiannoutsos, C., Ansari, R., Fox, E., Fisch, M.J. et al. (2005) Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study. J Clin Oncol23: 1185-1191.
19.
Linardou, H., Aravantinos, G., Efstathiou, E., Kalofonos, C., Anagnostopoulos, A., Deliveliotis, C. et al. (2004) Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: phase II study of the Hellenic Co-operative Oncology Group. Urol64: 479-484.
20.
Loehrer Sr, P.J., Einhorn, L.H., Elson, P.J., Crawford, E.D., Keubler, P., Tannock, I. et al. (1992) A randomized comparison of cisplatin alone or in combination with methtrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol10: 1066-1073.
21.
Logothetis, C.J., Dexeus, F.H., Finn, L., Sella, A., Amato, R.J., Ayala, A.G. et al. (1990) A prospective randomized trial comparing M-VAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol8: 1050-1055.
22.
Meluch, A.A., Greco, F.A., Burris III, H.A., O’Rourke, T., Ortega, G., Steis, R.G. et al. (2001) Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol19: 3018-3024.
23.
Moore, M.J., Tannock, I.F., Ernst, D.S., Huan, S. and Nevin, M. ( 1997) Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer. J Clin Oncol15: 3441-3445.
24.
Moore, M.J., Winquist, E.W., Murray, N., Tannock, I.F., Huan, S., Bennett, K. et al. (1999) Gemcitabine plus cisplatin, an active regimen in advanced urothelial cancer: a phase II trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol17: 2876-2881.
25.
Nogué-Aliguer, M., Carles, J., Arrivi, A., Juan, O., Alonso, L., Font, A. et al. (2003) Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. Cancer97: 2180-2186.
26.
Petrioli, R., Frediani, B., Manganelli, A., Barbanti, G., De Capua, B., De Lauretis, A. et al. (1996) Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients. Cancer77: 344-351.
27.
Ricci, S., Galli, L., Chioni, A., Iannopollo, M., Antonuzzo, A., Francesca, F. et al. (2002) Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum-based regimens . Cancer95: 1444-1450.
28.
Saxman, S.B., Propert, K.J., Einhorn, L.H., Crawford, E.D., Tannock, I., Raghavan, D. et al. (1997) 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 Oncol15: 2564-2569.
29.
Shipley, W.U., Kaufman, D.S. and McDougal, W.S. ( 2008) Cancers of the genitourinary system, In: DeVita, V.T., Hellman, S. and Rosenberg, S.A. (eds). Cancer: Practice and Principles in Oncology, Lippincott and Williams: Philadelphia, PA.
30.
Small, E.J., Lew, D., Redman, B.G., Petrylak, D.P., Hammond, N., Gross, H.M. et al. (2000) Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: the importance of survival as clinical trial end point. J Clin Oncol18: 2537-2544.
31.
Stadler, W.M., Kuzel, T., Roth, B., Raghavan, D. and Dorr, F.W. ( 1997) Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol15: 3394-3398.
32.
Sternberg, C.N., Yagoda, A., Scher, H.I., Watson, R.C., Geller, N., Herr, H.W. et al. (1989) Methotrexate, vinblastine, doxorubicin and cisplatin for advanced transitional cell carcinoma of the urothelium. Cancer64: 2448-2458.
33.
Türkölmez, K., Bedük, Y., Baltaci, S., Göğüş, C. and Göğüş , O. (2003) Gemcitabine plus vinorelbine chemotherapy in patients with advanced bladder carcinoma who are medically unsuitable for or who have failed cisplatin-based chemotherapy. Eur Urol44: 682-686.
34.
Vaughn, D.J., Manola, J., Dreicer, R., See, W., Levitt, R. and Wilding, G. ( 2002) Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer95: 1022-1027.
35.
von der Maase, H., Hansen, S.W., Roberts, J.T., Dogliotti, L., Oliver, T., Moore, M.J. et al. (2000) 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 Oncol17: 3068-3077.
36.
von der Maase, H., Lehmann, J., Gravis, G., Joensuu, H., Geertsen, P.F., Gough, J. et al. (2006) A phase II trial of pemetrexed plus gemcitabine in locally advanced and/or metastatic transitional cell carcinoma of the urothelium . Ann Oncol17: 1533-1538.
