• Toni K Choueiri, Susanna Jacobus, Joaquim Bellmunt, Angela Qu, Leonard J Appleman, Christopher Tretter, Glenn J Bubley, Edward C Stack, Sabina Signoretti, Meghara Walsh, Graeme Steele, Michelle Hirsch, Christopher J Sweeney, Mary-Ellen Taplin, Adam S Kibel, Katherine M Krajewski, Philip W Kantoff, Robert W Ross, and Jonathan E Rosenberg.
• Toni K. Choueiri, Susanna Jacobus, Joaquim Bellmunt, Angela Qu, Edward C. Stack, Sabina Signoretti, Meghara Walsh, Graeme Steele, Michelle Hirsch, Christopher J. Sweeney, Mary-Ellen Taplin, Adam S. Kibel, Katherine M. Krajewski, Philip W. Kantoff, Robert W. Ross, and Jonathan E. Rosenberg, Dana-Farber Cancer Institute and Brigham and Women's Hospital; Christopher Tretter, Lahey Clinic, Burlington; Glenn J. Bubley, Beth Israel Deaconess Medical Center, Boston, MA; Leonard J. Appleman, University of Pittsburgh, Pittsburgh, PA; and Jonathan E. Rosenberg, Memorial Sloan-Kettering Cancer Center, New York, NY. toni_choueiri@dfci.harvard.edu.
• J. Clin. Oncol. 2014 Jun 20;32(18):1889-94.

PurposeIn advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscle-invasive urothelial cancer (MIUC).Patients And MethodsPatients with cT2-cT4, N0-1, M0 MIUC were enrolled. Four cycles of ddMVAC were administered, followed by radical cystectomy. The primary end point was pathologic response (PaR) defined by pathologic downstaging to ≤ pT1N0M0. The study used Simon's optimal two-stage design to evaluate null and alternative hypotheses of PaR rate of 35% versus 55%. Secondary end points included toxicity, disease-free survival (DFS), radiologic response (RaR), and biomarker correlates, including ERCC1.ResultsBetween December 2008 and April 2012, 39 patients (cT2N0, 33%; cT3N0, 18%; cT4N0, 3%; cT2-4N1, 43%; unspecified, 3%) were enrolled. Median follow-up was 2 years. Overall, 49% (80% CI, 38 to 61) achieved PaR of ≤ pT1N0M0, and we concluded this regimen was effective. High-grade (grade ≥ 3) toxicities were observed in 10% of patients, with no neutropenic fevers or treatment-related death. One-year DFS was 89% versus 67% for patients who achieved PaR compared with those who did not (hazard ratio [HR], 2.6; 95% CI, 0.8 to 8.1; P = .08) and 86% versus 62% for patients who achieved RaR compared with those who did not (HR, 4.1; 95% CI, 1.3 to 12.5; P = .009). We found no association between serum tumor markers or ERCC1 expression with response or survival.ConclusionIn patients with MIUC, neoadjuvant ddMVAC was well tolerated and resulted in significant pathologic and radiologic downstaging.© 2014 by American Society of Clinical Oncology.

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