Skip to main content
Erschienen in: International Journal of Clinical Oncology 1/2017

17.08.2016 | Original Article

The utility of neoadjuvant gemcitabine plus carboplatin followed by immediate radical cystectomy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy

verfasst von: Hiromi Murasawa, Takuya Koie, Chikara Ohyama, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Ikuya Iwabuchi, Masaru Ogasawara, Toshiaki Kawaguchi

Erschienen in: International Journal of Clinical Oncology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

There are currently no data supporting carboplatin-based regimens in muscle-invasive bladder cancer patients who are unsuitable for neoadjuvant cisplatin treatment. The aim of this study was to investigate the potential benefit of carboplatin-based regimens in patients with muscle-invasive bladder cancer who were unsuitable for cisplatin.

Methods

We focused on 171 patients ineligible for cisplatin, including 98 patients who received neoadjuvant gemcitabine and carboplatin (GCarbo) followed by immediate radical cystectomy (GCarbo cohort) and 73 patients who underwent radical cystectomy (RC alone cohort) at Hiroaki University or Aomori Prefectural Hospital. In the neoadjuvant GCarbo cohort, patients underwent two 21-day cycles of GCarbo the two courses of neoadjuvant chemotherapy were followed by radical cystectomy at an interval of 1 month.

Results

Of the enrolled patients, 165 (95.3 %) had renal impairment. The median age of the enrolled patients was 71 years, and the median follow-up period was 63 months. The 5-year overall survival rates for the GCarbo and the RC-alone cohorts were 79.5 and 53.8 %, respectively (P < 0.001), while the 5-year disease-free survival rates were 75.5 and 55.4 %, respectively (P = 0.013). Surgical specimens of 16 (16.3 %) patients in the GCarbo cohort indicated stage pT0 disease. The rate of positive surgical margins in the RC-alone cohort was significantly higher than that in the GCarbo cohort (P < 0.001).

Conclusions

In this study, the oncological outcomes were significantly improved in cisplatin-unfit patients with muscle-invasive bladder cancer who received neoadjuvant GCarbo chemotherapy, compared with those in patients who underwent RC alone. The standard of care for muscle-invasive bladder cancer, especially for patients who are unfit for cisplatin, may include neoadjuvant carboplatin chemotherapy followed by radical cystectomy.
Literatur
1.
Zurück zum Zitat Witjes JA, Compérat E, Cowan NC et al (2014) EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 65:778–792CrossRefPubMed Witjes JA, Compérat E, Cowan NC et al (2014) EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 65:778–792CrossRefPubMed
3.
Zurück zum Zitat Grossman HB, Natale RB, Tangen CM et al (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Eng J Med 349:859–866CrossRef Grossman HB, Natale RB, Tangen CM et al (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Eng J Med 349:859–866CrossRef
4.
Zurück zum Zitat International Collaboration of Trial on behalf of the Medical Research Council Advanced Bladder Cancer Working Party (2011) 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 29:2171–2177CrossRef International Collaboration of Trial on behalf of the Medical Research Council Advanced Bladder Cancer Working Party (2011) 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 29:2171–2177CrossRef
5.
Zurück zum Zitat Advanced Bladder Cancer Meta-analysis Collaboration (2003) Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361:19271934 Advanced Bladder Cancer Meta-analysis Collaboration (2003) Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361:19271934
6.
Zurück zum Zitat Scosyrev E, Messing EM, van Wijngaarden E et al (2012) Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder. Cancer 118:72–81CrossRefPubMed Scosyrev E, Messing EM, van Wijngaarden E et al (2012) Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder. Cancer 118:72–81CrossRefPubMed
7.
Zurück zum Zitat Mertens LS, Meijer RP, Kerst JM et al (2012) Carboplatin based induction chemotherapy for nonorgan confined bladder cancer—a reasonable alternative for cisplatin unfit patients? J Urol 188:1108–1113CrossRefPubMed Mertens LS, Meijer RP, Kerst JM et al (2012) Carboplatin based induction chemotherapy for nonorgan confined bladder cancer—a reasonable alternative for cisplatin unfit patients? J Urol 188:1108–1113CrossRefPubMed
8.
Zurück zum Zitat von der Masse H, Sengelov L, Roberts JT 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. J Clin Oncol 23:4602–4608CrossRef von der Masse H, Sengelov L, Roberts JT 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. J Clin Oncol 23:4602–4608CrossRef
9.
Zurück zum Zitat Dash A, Galsky MD, Vickers AJ et al (2006) Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer 107:506–513CrossRefPubMed Dash A, Galsky MD, Vickers AJ et al (2006) Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer 107:506–513CrossRefPubMed
10.
Zurück zum Zitat Grubmueller B, Seitz C, Shariat SF (2016) The treatment of muscle-invasive bladder cancer in geriatric patients. Curr Opin Urol 26:160–164CrossRefPubMed Grubmueller B, Seitz C, Shariat SF (2016) The treatment of muscle-invasive bladder cancer in geriatric patients. Curr Opin Urol 26:160–164CrossRefPubMed
11.
Zurück zum Zitat De Santis M, Bellmunt J, Mead G et al (2012) 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 30:191–199CrossRefPubMed De Santis M, Bellmunt J, Mead G et al (2012) 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 30:191–199CrossRefPubMed
12.
Zurück zum Zitat Bellmunt J, Ribas A, Eres N et al (1997) Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma. Cancer 80:1966–1972CrossRefPubMed Bellmunt J, Ribas A, Eres N et al (1997) Carboplatin-based versus cisplatin-based chemotherapy in the treatment of surgically incurable advanced bladder carcinoma. Cancer 80:1966–1972CrossRefPubMed
13.
Zurück zum Zitat Dogliotti L, Cartenì G, Siena S 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 Urol 52:134–141CrossRefPubMed Dogliotti L, Cartenì G, Siena S 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 Urol 52:134–141CrossRefPubMed
14.
Zurück zum Zitat Galsky MD, Hahn NM, Rosenberg G et al (2011) Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol 14:2432–2438CrossRef Galsky MD, Hahn NM, Rosenberg G et al (2011) Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy. J Clin Oncol 14:2432–2438CrossRef
15.
Zurück zum Zitat Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756PubMed Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748–1756PubMed
16.
Zurück zum Zitat Koie T, Ohyama C, Yamamoto H et al (2012) Minimum incision endoscopic radical cystectomy in patients with malignant tumors of the urinary bladder: clinical and oncological outcomes at a single institution. Eur J Surg Oncol 38:1101–1105CrossRefPubMed Koie T, Ohyama C, Yamamoto H et al (2012) Minimum incision endoscopic radical cystectomy in patients with malignant tumors of the urinary bladder: clinical and oncological outcomes at a single institution. Eur J Surg Oncol 38:1101–1105CrossRefPubMed
17.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMed
18.
Zurück zum Zitat American Joint Committee on Cancer (AJC) (2010) Urinary bladder. In: Edge SB, Byrd DR, Compton CC et al (eds) AJCC cancer staging manual, 7th edn. Springer, New York, pp 497–505CrossRef American Joint Committee on Cancer (AJC) (2010) Urinary bladder. In: Edge SB, Byrd DR, Compton CC et al (eds) AJCC cancer staging manual, 7th edn. Springer, New York, pp 497–505CrossRef
19.
Zurück zum Zitat Hautman RE, de Petriconi RC, Pfeiffer C et al (2012) Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 61:1039–1047CrossRef Hautman RE, de Petriconi RC, Pfeiffer C et al (2012) Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 61:1039–1047CrossRef
20.
21.
Zurück zum Zitat Koie T, Ohyama C, Hashimoto Y et al (2013) Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study. Int J Clin Oncol 18:724–730CrossRefPubMed Koie T, Ohyama C, Hashimoto Y et al (2013) Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study. Int J Clin Oncol 18:724–730CrossRefPubMed
22.
Zurück zum Zitat Galsky MD, Chen GJ, Oh WK et al (2012) Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol 23:406–410CrossRefPubMed Galsky MD, Chen GJ, Oh WK et al (2012) Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol 23:406–410CrossRefPubMed
23.
Zurück zum Zitat Kim YR, Lee JL, You D et al (2015) Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol 76:141–153CrossRefPubMed Kim YR, Lee JL, You D et al (2015) Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol 76:141–153CrossRefPubMed
24.
Zurück zum Zitat Dash A, Pettus JA 4th, Herr HW et al (2008) A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 113:2471–2477CrossRefPubMedPubMedCentral Dash A, Pettus JA 4th, Herr HW et al (2008) A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 113:2471–2477CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Weight CJ, Garcia JA, Hansel DE et al (2009) Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder. A contemporary series. Cancer 115:792–799CrossRefPubMed Weight CJ, Garcia JA, Hansel DE et al (2009) Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder. A contemporary series. Cancer 115:792–799CrossRefPubMed
Metadaten
Titel
The utility of neoadjuvant gemcitabine plus carboplatin followed by immediate radical cystectomy in patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy
verfasst von
Hiromi Murasawa
Takuya Koie
Chikara Ohyama
Hayato Yamamoto
Atsushi Imai
Shingo Hatakeyama
Takahiro Yoneyama
Yasuhiro Hashimoto
Ikuya Iwabuchi
Masaru Ogasawara
Toshiaki Kawaguchi
Publikationsdatum
17.08.2016
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 1/2017
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-016-1029-2

Weitere Artikel der Ausgabe 1/2017

International Journal of Clinical Oncology 1/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.