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Plimack ER , Hoffman-Censits JH , Viterbo R , Trabulsi EJ , Ross EA , Greenberg RE , Chen DY , Lallas CD , Wong YN , Lin J , Kutikov A , Dotan E , Brennan TA , Palma N , Dulaimi E , Mehrazin R , Boorjian SA , Kelly WK , Uzzo RG , Hudes GR
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
J Clin Oncol. 2014 Jun 20;32(18) :1895-901
PMID: 24821881    PMCID: PMC4050203    URL: https://www.ncbi.nlm.nih.gov/pubmed/24821881
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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.
Plimack, Elizabeth R Hoffman-Censits, Jean H Viterbo, Rosalia Trabulsi, Edouard J Ross, Eric A Greenberg, Richard E Chen, David Y T Lallas, Costas D Wong, Yu-Ning Lin, Jianqing Kutikov, Alexander Dotan, Efrat Brennan, Timothy A Palma, Norma Dulaimi, Essel Mehrazin, Reza Boorjian, Stephen A Kelly, William Kevin Uzzo, Robert G Hudes, Gary R eng P30 CA006927/CA/NCI NIH HHS/ P30 CA056036/CA/NCI NIH HHS/ 3 P30 CA-006927-47S4/CA/NCI NIH HHS/ P30CA00692/CA/NCI NIH HHS/ Clinical Trial, Phase II Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Clin Oncol. 2014 Jun 20;32(18):1895-901. doi: 10.1200/JCO.2013.53.2465. Epub 2014 May 12.