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

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• 作者：Takuya Koie (1)
  Chikara Ohyama (1)
  Yasuhiro Hashimoto (1)
  Shingo Hatakeyama (1)
  Hayato Yamamoto (1)
  Takahiro Yoneyama (1)
  Noritaka Kamimura (1)
  
• 关键词：Neoadjuvant chemotherapy ; Radical cystectomy ; Urothelial carcinoma ; Gemcitabine ; Carboplatin
• 刊名：International Journal of Clinical Oncology
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：18
• 期：4
• 页码：724-730
• 全文大小：297KB
• 参考文献：1. Raghavan D, Shipley WU, Hall RR et al (1997) Biology and management of invasive bladder cancer. In: Raghavan D, Scher HI (eds) Principles and practice of genitourinary oncology. Lippincott-Ravel, Philadelphia, pp 281-98
  2. Ghonheim MA, El-Mekresh MM, Mokhtar AA et al (2000) A predictive model of survival after radical cystectomy for carcinoma of the bladder. BJU Int 85:811-16 CrossRef
  3. 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 349:859-66 CrossRef
  4. David KA, Milowsky MI, Ritchey J et al (2007) Low incidence of perioperative chemotherapy for stage III bladder cancer 1998-003: a report from the National Cancer Data Base. J Urol 178:451-54 CrossRef
  5. Loehrer P, Einhorn LH, Elson PJ et al (1992) A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a Cooperative Group Study. J Clin Oncol 10:1066-073
  6. Mamhmud S, Fong B, Fahmy N et al (2006) Effect of preoperative delay on survival in patients with bladder cancer undergoing cystectomy in Quebec: a population based study. J Urol 175:78-3 CrossRef
  7. 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 115:792-99 CrossRef
  8. von der Masse H, Sengelov L, Roberts JT et al (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large randomized, multicenter, multinational, multicenter, phase III study. J Clin Oncol 18:3068-077
  9. 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 23:4602-608 CrossRef
  10. Dash A, Pettus JA IV, Herr HW et al (2008) A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer 113:24712477 CrossRef
  11. 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 29:2171-177 CrossRef
  12. 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 80:1966-972 CrossRef
  13. Bamias A, Moulopoulos LA, Koutras A et al (2006) The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group. Cancer 106:297-03 CrossRef
  14. Galsky MD, Hahn NM, Rosenberg G et al (2011) Treatment of patients with metastatic urothelial cancer “unfit-for cisplatin-based chemotherapy. J Clin Oncol 14:2432-438 CrossRef
  15. Calvert AH, Newell DR, Gumbrell LA et al (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748-756
  16. Greene FL, Page DL, Fleming ID et al (2002) AJCC cancer staging manual, 6th edn. Springer, New York
  17. Life expectancy and mortality (2011). In: World health statistics 2011, World health organization press, Geneva, pp 45-5
  18. Koie T, Yamamoto H, Okamoto A et al (2009) Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer. J Clin Oncol 27(suppl):e16100
  19. Ranaldi M, Crino L, Scagliotti GV et al (2000) A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: a phase II randomized trial. Ann Oncol 11:1295-300 CrossRef
  20. Para HS, Caviuna R, Latteri F et al (2004) Tree-week versus four-week schedule of cisplatin and gemcitabine: results of randomized phase II study. Ann Oncol 13:1080-086 CrossRef
  21. Ando Y, Minami H, Saka H et al (1997) Adjustment of creatinine clearance improves accuracy of Calvert’s formula for carboplatin dosing. Br J Cancer 76:1067-071 CrossRef
  22. Advanced Bladder Cancer Meta-analysis Collaboration (2003) Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361:1927-934 CrossRef
  23. No authors listed (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomized controlled trial. International collaboration of trialists. Lancet 354:533-40 CrossRef
  24. Scosyrev E, Messing EM, van Wijngaarden E et al (2012) Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder. Cancer 118:72-1 CrossRef
  25. Shannon C, Crombie C, Brooks A et al (2001) Carboplatin and gemcitabine in metastatic transitional cell carcinoma of the urothelium: effective treatment of patients with poor prognostic feature. Ann Oncol 12:947-52 CrossRef
  26. Linardou H, Aravantinos G, Efstathiou E 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. Urology 64:479-84 CrossRef
  
• 作者单位：Takuya Koie (1)
  Chikara Ohyama (1)
  Yasuhiro Hashimoto (1)
  Shingo Hatakeyama (1)
  Hayato Yamamoto (1)
  Takahiro Yoneyama (1)
  Noritaka Kamimura (1)
  
  1. Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan
  

文摘

Background Neoadjuvant cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer (BC) has better survival benefit than radical cystectomy (RC) alone. However, optimal dosing schedule, including drug selection, number of cycles, and interval between chemotherapy and cystectomy, as well as acceptable regimens remain to be established. We conducted a single-arm prospective study to evaluate efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarbo) chemotherapy followed by immediate RC in patients with muscle-invasive BC, including cisplatin-unfit patients. Methods Between March 2005 and June 2011, we enrolled 116 patients with histologically proven muscle-invasive BC, including 44?% of the patients who were identified as cisplatin-unfit. All participants received two courses of GCarbo therapy, gemcitabine 800?mg/m2 administered on days 1, 8, and 15 and carboplatin with an area under the curve of four (AUC 4) administered on day 2. RC and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. The primary endpoint was pT0 in the cystectomy specimen. Secondary endpoints were overall response rate, overall (OS) and disease-free survival (DFS), and toxicity. Survival after cystectomy was analyzed using the Kaplan–Meier method. Results The RC specimens of 28 (24.1?%) patients showed pT0. At a median follow-up period of 41?months, the OS and DFS rates were 89.7 and 86.3?%, respectively. No patients had grade 3/4 gastrointestinal toxicity or renal impairment. Conclusions Neoadjuvant GCarbo therapy followed by immediate RC is safe, even in cisplatin-unfit patients, and provides a favorable pathological cancer-free state. The single-arm single-institution study design and relatively short observation period were limitations of this study.