A dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) followed by cystectomy may be a more effective treatment option than standard neoadjuvant chemotherapy (NAC) among patients with bladder cancer, according to a study published in JAMA Oncology.1

The standard of care for patients with muscle-invasive bladder is NAC before cystectomy, and gemcitabine plus cisplatin is among the most frequently used regimens. Previous studies have shown that ddMVAC is well tolerated, but how it compares with gemcitabine plus cisplatin in regard to cancer control and survival outcomes requires further investigation.

For this cross-sectional analysis, researchers evaluated the outcomes of 1113 patients with bladder cancer who underwent cystectomy. A total of 824 patients had invasive or advanced-stage disease, of whom 40.3% (332) received NAC; 61.4%, 10%, and 14.0% received gemcitabine-cisplatin, gemcitabine-carboplatin, and ddMVAC, respectively.

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Results showed that patients who received ddMVAC had a downstaging rate of 52.2%, compared with 41.3% for gemcitabine-cisplatin and 27.0% for gemcitabine-carboplatin.

The complete response rate for ddMVAC was 41.3%, compared with 24.5% for gemcitabine-cisplatin and 9.4% for gemcitabine-carboplatin (P < .001).

Adjusted analyses revealed that ddMVAC had a higher likelihood of downstaging (odds ratio [OR], 1.84; 95% CI, 1.10-3.09) and complete response (OR, 2.67; 95% CI, 1.50-4.77) compared with gemcitabine-cisplatin; propensity score matching demonstrated similar results.

Patients treated with ddMVAC also had improved overall survival compared with patients who received other NAC regimens, but this finding did not reach statistical significance upon adjustment or in propensity-matched models (hazard ratio [HR], 0.44; 95% CI, 0.14-1.38; P = .16).

Findings suggest that ddMVAC may lead to improved outcomes in this patient population compared to standard NAC. The authors concluded that the data highlight “the need to further investigate ddMVAC vs standard NAC in a prospective, randomized fashion.”


  1. Peyton CC, Tang D, Reich RR, et al. Downstaging and survival outcomes associated with neoadjuvant chemotherapy regimens among patients treated with cystectomy for muscle-invasive bladder cancer [published online August 30, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.3542