Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91658
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Type: Journal article
Title: Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates
Author: Choueiri, T.
Jacobus, S.
Bellmunt, J.
Qu, A.
Appleman, L.
Tretter, C.
Bubley, G.
Stack, E.
Signoretti, S.
Walsh, M.
Steele, G.
Hirsch, M.
Sweeney, C.
Taplin, M.
Kibel, A.
Krajewski, K.
Kantoff, P.
Ross, R.
Rosenberg, J.
Citation: Journal of Clinical Oncology, 2014; 32(18):1889-1894
Publisher: American Society of Clinical Oncology
Issue Date: 2014
ISSN: 0732-183X
1527-7755
Statement of
Responsibility: 
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
Abstract: PURPOSE: In 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 METHODS: Patients 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. RESULTS: Between 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. CONCLUSION: In patients with MIUC, neoadjuvant ddMVAC was well tolerated and resulted in significant pathologic and radiologic downstaging.
Keywords: Carcinoma, Transitional Cell; Cisplatin; Methotrexate; Doxorubicin; Vinblastine; Endonucleases; DNA-Binding Proteins; Recombinant Proteins; Magnetic Resonance Imaging; Protective Agents; Disease-Free Survival; Treatment Outcome; Chemotherapy, Adjuvant; Neoadjuvant Therapy; Cystectomy; Drug Administration Schedule; Tumor Markers, Biological; Neoplasm Staging; Urinary Bladder Neoplasms; Aged, 80 and over; Immunohistochemistry; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor; Neoplasm Invasiveness; Kaplan-Meier Estimate
Description: Presented in part at the 2013 Genitourinary Cancers Symposium, Orlando, FL, February 14-16, 2013, and 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013.
Rights: © 2014 by American Society of Clinical Oncology
RMID: 0030029184
DOI: 10.1200/JCO.2013.52.4785
Appears in Collections:Medicine publications

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