Neoadjuvant Dose-Dense MVAC May Improve Post-Cystectomy Outcomes

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Neoadjuvant dose-dense MVAC prior to radical cystectomy may be a better option than conventional regimens for patients with muscle-invasive bladder cancer.
Neoadjuvant dose-dense MVAC prior to radical cystectomy may be a better option than conventional regimens for patients with muscle-invasive bladder cancer.

Neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) using a dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) is associated with better outcomes after radical cystectomy than standard NAC, according to a recent study.

The study compared ddMVAC with gemcitabine-cisplatin, gemcitabine-carboplatin, and other NAC regimens in 46, 204, 32, and 50 patients, respectively. A team led by Scott M. Gilbert, MD, MS, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida documented downstaging to pT0N0 (complete pathologic response) in 41.3% of ddMVAC recipients compared with 24.5%, 9.4%, and 24% of patients who received gemcitabine-cisplatin, gemcitabine-carboplatin, and other NAC regimens, respectively. Compared with gemcitabine-cisplatin (reference), ddMVAC was associated with significant 2.7-fold increased adjusted odds of downstaging to pT0N0, Dr Gilbert and his colleagues reported online ahead of print in JAMA Oncology.

In addition, the proportion of patients who experienced any downstaging was 52.2% in the ddMVAC group compared with 41.3%, 27%, and 42% in the gemcitabine-cisplatin, gemcitabine-carboplatin, and other NAC arms, respectively. Compared with gemcitabine-cisplatin treatment, ddMVAC treatment was associated with significant 1.8-fold higher adjusted odds of any downstaging.

Adverse effects associated with MVAC, such as fatigue, nausea, and vomiting, have limited its widespread is widespread use to date, Dr Gilbert and colleagues noted. Consequently, the combination of gemcitabine with cisplatin is more commonly used prior to cystectomy.

“Although gemcitabine with cisplatin is the most frequently prescribed neoadjuvant chemotherapy regimen for patients with muscle-invasive bladder cancer, for eligible patients, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin may led to better outcomes,” the authors wrote.

Reference

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. JAMA Oncol. 2018; published online ahead of print.

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