Triplet chemotherapy with paclitaxel, gemcitabine, and cisplatin as second-line therapy for advanced urothelial carcinoma


Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment for patients who fail these firstline chemotherapies is unavailable. We examined the efficacy and safety of secondline paclitaxel, gemcitabine, and cisplatin (PCG) chemotherapy in Japanese patients. Methods: Between 2004 and 2010, 25 patients with metastatic UCs who failed to respond to platinumbased regimens were treated with PCG. They received intravenous paclitaxel (60 mg/m2) and gemcitabine (1000 mg/m2) on days 1 and 8, and cisplatin (70 mg/m2) on day 2 of every 21 day course. We retrospectively collected patients’ clinical and pathological data and evaluated adverse effects and survivals. Results: Patients underwent 95 PCG cycles in all (average, 3.8 cycles per patient). One patient (4%) achieved complete response, 5 (20%) showed partial response, 8 (42%) had disease stabilization, and 5 (26%) had disease progression. Median overall survival was 8.5 months. Neutropenia and thrombocytopenia of grade ≥ 3 were observed in 68% and 56% of patients, respectively. No treatment related death occurred. Multivariate analysis revealed that hemoglobin levels < 10 g/dL and estimated glomerular filtration rate < 60 mL/(min1.73 m2) were significant risk factors for overall survival. Conclusion: PCG chemotherapy in the secondline setting potentially contributed to good prognosis in selected patients with relatively significant but tolerable toxicity.

Share and Cite:

Takeshita, H., Chiba, K., Kitayama, S., Moriyama, S., Omura, R. and Noro, A. (2013) Triplet chemotherapy with paclitaxel, gemcitabine, and cisplatin as second-line therapy for advanced urothelial carcinoma. Modern Chemotherapy, 2, 1-7. doi: 10.4236/mc.2013.21001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Loehrer, P.J., Sr, Einhorn, L.H., Elson, P.J., Crawford, E.D., Kuebler, P., Tannock, I., et al. (1992) A randomized comparison of cisplatin alone or in combination with me- thotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group stu- dy. Journal of Clinical Oncology, 10, 1066-1073.
[2] 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 car- cinoma: a cooperative group study. Journal of Clinical Oncology, 15, 2564-2569.
[3] von der Maase, H., Sengelov, L., Roberts, J.T., Ricci, S., Dogliotti, L., Oliver, T., et al. (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of Cli- nical Oncology, 23, 4602-4608. doi:10.1200/JCO.2005.07.757
[4] Sternberg, C.N., Calabrò, F., Pizzocaro, G., Marini, L., Schnetzer, S., Sella, A. (2001) Chemotherapy with an every-2-week regimen of gemcitabine and paclitaxel in patients with transitional cell carcinoma who have re- ceived prior cisplatin-based therapy. Cancer, 92, 2993- 2998. doi:10.1002/1097-0142(20011215)92:12<2993::AID-CNCR10108>3.0.CO;2-2
[5] Fechner, G., Siener, R., Reimann, M., Kobalz, L., Albers, P. (2006) Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with tran- sitional cell carcinoma (AUO Trial AB 20/99). The In- ternational Journal of Clinical Practice, 60, 27-31. doi:10.1111/j.1742-1241.2005.00663.x
[6] Matsumoto, K., Irie, A., Satoh, T., Okazaki, M., Iwamura, M., Baba, S. (2007) Gemcitabine and paclitaxel chemo- therapy as a second-line treatment for advanced or me- tastatic urothelial carcinoma. International Journal of Urology, 14, 1000-1004.
[7] Kanai, K., Kikuchi, E., Ohigashi, T., Miyajima, A., Na- kagawa, K., Nakashima, J., et al. (2008) Gemcitabine and paclitaxel chemotherapy for advanced urothelial carci- noma in patients who have received prior cisplatin-based chemotherapy. International Journal of Clinical Onco- logy, 13, 510-514. doi:10.1007/s10147-008-0779-x
[8] Culine, S., Theodore, C., De Santis, M., Bui, B., Demkow, T., Lorenz, J., et al. (2006) A phase II study of vinflunine in bladder cancer patients pro?gressing after first-line pla- tinum-containing regimen. British Journal of Cancer, 94, 1395-1401. doi:10.1038/sj.bjc.6603118
[9] Bellmunt, J., Théodore, C., Demkov, T., Komyakov, B., Sengelov, L., Daugaard, G., et al. (2009) 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. Journal of Clinical Oncology, 27, 4454-4461. doi:10.1200/JCO.2008.20.5534
[10] Bellmunt, J., Guillem, V., Paz-Ares, L., González-Larriba, J.L., Carles, J., Batiste-Alentorn, E., et al. (2000) Phase I-II study of paclitaxel, cisplatin, and gemcitabine in ad- vanced transitional-cell carcinoma of the urothelium. Journal of Clinical Oncology, 18, 3247-3255.
[11] Bellmunt, J., von der Maase, H., Mead, G.M., Skoneczna, I., De Santis, M., Daugaard, G., et al. (2012) Randomized phase III study comparing paclitaxel/cisplatin/gemcit- abine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. Jour- nal of Clinical Oncology, 30, 1107-1113.
[12] Charlson, M.E., Pompei, P., Ales, K.L., MacKenzie, C.R. (1987) A new method of classifying prognostic comor- bidity in longitudinal studies: Development and valida- tion. Journal of Chronic Diseases, 40, 373-383.
[13] Romano, P.S., Roos, L.L., Jollis, J.G. (1993) Adapting a clinical comorbidity index for use with ICD-9-CM ad- ministrative data: differing perspectives. Journal of Clini- cal Epidemiology, 46, 1075-1079.
[14] Matsuo, S., Imai, E., Horio, M., Yasuda, Y., Tomita, K., Nitta, K., et al. (2009) Revised equations for estimated GFR from serum creatinine in Japan. American Journal of Kidney Diseases, 53, 982-992. doi:10.1053/j.ajkd.2008.12.034
[15] Therasse, P., Arbucl, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, L., et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. Journal of the National Cancer Institute. 92, 205-216.
[16] Fukui, I., Yonese, J., Tsukamoto, T., Yoshida, T., Kim, T., Tohma, T., et al. (2001) Combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin for me- mtastatic urothelial cancer. Cancer Chemotherapy and Pharmacology, 48, 88-93.
[17] Tatokoro, M., Kawakami, S., Yonese, J., Fujii, Y., Okubo, Y., Yamamoto, S., et al. (2008) Preliminary report of mul- timodal treatment with ifosfamide, 5-fluorouracil, eto- poside and cisplatin (IFEP chemotherapy) against metas- tatic adenocarcinoma of the urachus. International Jour- nal of Urology, 15, 851-853. doi:10.1111/j.1442-2042.2008.02113.x
[18] Bellmunt, J., Albanell, J., Paz-Ares, L., Climent, M.A., González-Larriba, J.L., Carles, J., et al. (2002) Pretreat- ment prognostic factors for survival in patients with- advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer, 95, 751-757. doi:10.1002/cncr.10762
[19] Bellmunt, J., Choueiri, T.K., Fougeray, R., Schutz, F.A., Salhi, Y., Winquist, E., et al. (2010) Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with plati- num-containing regimens. Journal of Clinical Oncology, 28, 1850-1855. doi:10.1200/JCO.2009.25.4599
[20] Saito, K., Urakami, S., Komai, Y., Yasuda, Y., Kubo, Y., Kitsukawa, S., et al. (2012) Impact of C-reactive protein kinetics on survival of patients with advanced urothelial carcinoma treated by second-line chem?otherapy with gemcitabine, etoposide and cisplatin. BJU International, 110, 1478-1484. doi:10.1111/j.1464-410X.2012.11153.x
[21] Thrasher, J.B., Frazier, H.A., Robertson, J.E., Dodge, R.K., Paulson, D.F. (1994) Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell car- cinoma of the bladder and prostate. Cancer, 73, 1708- 1715. doi:10.1002/1097-0142(19940315)73:6<1708::AID-CNCR2820730626>3.0.CO;2-J
[22] Orita, Y., Gejyo, F., Sakatsume, M., Shiigai, T., Maeda, Y., Imai, E., et al. (2005) Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clea- rance (article in Japanese). Nihon Jinzo Gakkai Shi, 47, 804-812.
[23] Paz-Ares, L.G., Solsona, E., Esteban, E., Saez, A., Gon- zalez-Larriba, J., Anton, A., et al. (2010) Randomized phase III trial comparing adjuvant paclitaxel/gemcita- bine/cisplatin (PGC) to observation in patients with re- sected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. Journal of Clinical Oncology, 28, 18s.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.