Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Is Safe, Effective, and Efficient Neoadjuvant Treatment for Muscle-Invasive Bladder Cancer: Results of a Multicenter Phase II Study With Molecular Correlates of Response and Toxicity

被引:220
作者
Plimack, Elizabeth R. [1 ]
Hoffman-Censits, Jean H. [2 ]
Viterbo, Rosalia [1 ]
Trabulsi, Edouard J. [2 ]
Ross, Eric A. [1 ]
Greenberg, Richard E. [1 ]
Chen, David Y. T. [1 ]
Lallas, Costas D. [2 ]
Wong, Yu-Ning [1 ]
Lin, Jianqing [2 ]
Kutikov, Alexander [1 ]
Dotan, Efrat [1 ]
Brennan, Timothy A. [3 ]
Palma, Norma [3 ]
Dulaimi, Essel [1 ]
Mehrazin, Reza [1 ]
Boorjian, Stephen A. [4 ]
Kelly, William Kevin [2 ]
Uzzo, Robert G. [1 ]
Hudes, Gary R. [1 ]
机构
[1] Fox Chase Canc Ctr, Temple Hlth, Philadelphia, PA 19111 USA
[2] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA
[3] Fdn Med, Cambridge, MA USA
[4] Mayo Clin, Rochester, MN USA
关键词
TRANSITIONAL-CELL-CARCINOMA; UROTHELIAL CARCINOMA; RADICAL CYSTECTOMY; CHEMOTHERAPY; TRIAL; OVEREXPRESSION; COMPLICATIONS; GEMCITABINE; UPDATE;
D O I
10.1200/JCO.2013.53.2465
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls. Patients and Methods Patients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity. Results Forty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non-muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity. Conclusion AMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy. (C) 2014 by American Society of Clinical Oncology.
引用
收藏
页码:1895 / 1901
页数:7
相关论文
共 39 条
[1]   Neoadjuvant chemotherapy in invasive bladder cancer:: Update of a systematic review and meta-analysis of individual patient data [J].
Abol-Enein, H ;
Bassi, P ;
Boyer, M ;
Coppin, CML ;
Cortesi, E ;
Grossman, HB ;
Hall, RR ;
Horwich, A ;
Malmström, PU ;
Martinez-Piñeiro, JA ;
Sengelov, L ;
Sherif, A ;
Wallace, DMA ;
Bono, AV ;
Goebell, PJ ;
Groshen, S ;
Torti, FM ;
Clarke, NW ;
Roberts, JT ;
Sylvester, R ;
Parmar, MKB ;
Stewart, LA ;
Tierney, JF ;
Vale, CL .
EUROPEAN UROLOGY, 2005, 48 (02) :202-206
[2]  
[Anonymous], 1999, Lancet, V354, P533
[3]  
[Anonymous], J CLIN ONCOL
[4]   Kuhn's Paradigms: Are Those Closest to Treating Bladder Cancer the Last to Appreciate the Paradigm Shift? [J].
Bajorin, Dean F. ;
Herr, Harry W. .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (16) :2135-2137
[5]  
Beahrs OH, 1983, AJCC MANUAL STAGING
[6]   Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder [J].
Blick, Christopher ;
Hall, Peter ;
Pwint, Thinn ;
Al-Terkait, Faisal ;
Crew, Jeremy ;
Powles, Thomas ;
Macaulay, Valentine ;
Munro, Nicholas ;
Douglas, David ;
Kilbey, Neviana ;
Protheroe, Andrew ;
Chester, John D. .
CANCER, 2012, 118 (16) :3920-3927
[7]   Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the use of neoadjuvant chemotherapy [J].
Canter, Daniel ;
Long, Christopher ;
Kutikov, Alexander ;
Plimack, Elizabeth ;
Saad, Ismail ;
Oblaczynski, Megan ;
Zhu, Fang ;
Viterbo, Rosalia ;
Chen, David Y. T. ;
Uzzo, Robert G. ;
Greenberg, Richard E. ;
Boorjian, Stephen A. .
BJU INTERNATIONAL, 2011, 107 (01) :58-62
[8]   Telomere length measurement by a novel monochrome multiplex quantitative PCR method [J].
Cawthon, Richard M. .
NUCLEIC ACIDS RESEARCH, 2009, 37 (03)
[9]   Identification of Nine Genomic Regions of Amplification in Urothelial Carcinoma, Correlation with Stage, and Potential Prognostic and Therapeutic Value [J].
Chekaluk, Yvonne ;
Wu, Chin-Lee ;
Rosenberg, Jonathan ;
Riester, Markus ;
Dai, Qishan ;
Lin, Sharron ;
Guo, Yanan ;
McDougal, W. Scott ;
Kwiatkowski, David J. .
PLOS ONE, 2013, 8 (04)
[10]   The Clavien-Dindo Classification of Surgical Complications Five-Year Experience [J].
Clavien, Pierre A. ;
Barkun, Jeffrey ;
de Oliveira, Michelle L. ;
Vauthey, Jean Nicolas ;
Dindo, Daniel ;
Schulick, Richard D. ;
de Santibanes, Eduardo ;
Pekolj, Juan ;
Slankamenac, Ksenija ;
Bassi, Claudio ;
Graf, Rolf ;
Vonlanthen, Rene ;
Padbury, Robert ;
Cameron, John L. ;
Makuuchi, Masatoshi .
ANNALS OF SURGERY, 2009, 250 (02) :187-196