A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder

A retrospective experience

Authors

  • Atreya Dash MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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    • Atreya Dash was supported by a gift from the Tina and Richard V. Carolan Foundation.

    • Atreya Dash and Joseph A. Pettus, IV were supported by Training Grant T32–82088 from the National Institutes of Health.

  • Joseph A. Pettus IV MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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    • Atreya Dash and Joseph A. Pettus, IV were supported by Training Grant T32–82088 from the National Institutes of Health.

  • Harry W. Herr MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Bernard H. Bochner MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Guido Dalbagni MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • S. Machele Donat MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Paul Russo MD,

    1. Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Surgery, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Mary G. Boyle MD,

    1. Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Matthew I. Milowsky MD,

    1. Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York, New York
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  • Dean F. Bajorin MD

    Corresponding author
    1. Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial-Sloan Kettering Cancer Center, New York, New York
    2. Department of Medicine, Joan and Sanford Weill Medical College of Cornell University, New York, New York
    • Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021===

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    • Fax: (212) 988-1079


  • See editorial on pages 2379–81, this issue.

  • Presented in part at the American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, May 30-June 3, 2008.

Abstract

BACKGROUND.

Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment.

METHODS.

The authors retrospectively evaluated patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle-invasion (<pT2, ie, pT0, pTIS, pT1), chemotherapy delivery, and disease-free survival were the endpoints of interest. For comparison, similar endpoints were assessed in a historical cohort treated with neoadjuvant MVAC.

RESULTS.

Four cycles of neoadjuvant GC were given over 12 weeks (n = 42). Thirty-nine (93%) of 42 patients received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14-42), and no residual muscle-invasive disease proportion (<pT2) was 36% (95% CI, 21-52); pT0 was achieved in 28% (95% CI, 16-42) and <pT2 in 35% (95% CI, 23-49) of 54 MVAC-treated patients. All 15 GC patients achieving <pT2 pathologic stage remained disease-free at a median follow-up of 30 months.

CONCLUSIONS.

Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of GC-treated patients whose primary tumors were downstaged, with prolonged disease-free survival and minimal or no residual disease, was similar to MVAC-treated patients. Cancer 2008. © 2008 American Cancer Society.

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