Comparing Preoperative Chemotherapy Regimens in Patients with Muscle-Invasive Bladder Cancer - Expert Commentary

Neoadjuvant cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer (MIBC) before radical cystectomy improves overall survival. Commonly used neoadjuvant chemotherapy regimens include the combination of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or a combination of gemcitabine and cisplatin (GC).

The results of a recent randomized phase III  trial comparing response rates and toxicities between the dd-MVAC and GC regimens was published by Pfister et al. in European Urology. The study randomized 500 patients to either 6 cycles of dd-MVAC every 2 weeks or 4 cycles of GC every 3 weeks. Patients with primary bladder tumor histologically confirmed as urothelial carcinoma with no metastasis or lymph node involvement were eligible for the trial. 58% and 66% of patients completed treatment with dd-MVAC and GC, respectively.

In the dd-MVAC arm, 129 (52%) developed hematological toxicities, and asthenia was observed in 35 (14%) patients. In patients receiving the GC regimen, 134 (55%) patients developed hematological toxicities, while 10 (4.1%) reported asthenia. In addition, gastrointestinal disorders and severe anemia were observed more frequently in the dd-MVAC arm than in the GC arm.  Complete pathological responses (ypT0pN0) were similar in the dd-MVAC and GC arm (42% vs. 36, p=0.02). On the other hand, pathological downstaging (ypT1N0 or less) was higher in the dd-MVAC than GC arm (63% vs. 49%, p = 0.007).

As expected, fewer patients were able to complete 6 cycles of dd-MVAC compared to 4 cycles of GC. Therefore, adoption of a 6 cycle dd-MVAC regimen in the neoadjuvant setting is likely to be challenging. In addition, whether the higher local control rates observed in the trial on the dd-MVAC arm translate into better overall survival outcomes remains to be seen.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

Reference:

  1. Pfister C, Gravis G, Fléchon A, Soulié M, Guy L, Laguerre B, et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Seconda. Eur Urol. 2021 Feb;79(2):214–21.

Read the Abstract
email news signup