Clément Dumont1, Hélène Gauthier1, Pierre Mongiat-Artus2,3, Arnaud Daché3,4, François Jacob5, Denis Dadoun5, Damien Pouessel1, Vincent Ravery3,4, François Desgrandchamps2,3, Stéphane Culine1,3*
1Department of Medical Oncology, Saint-Louis Hospital, France
2Department of Urology, Saint-Louis Hospital, France
3Paris Diderot University, France 4Department of Urology, Bichat Hospital, France
5Clinique Saint-Faron, Mareuil-lès-Meaux, France
Background: Neoadjuvant cisplatin-based chemotherapy for Muscle-Invasive Bladder Cancer (MIBC) is supported by level 1 evidence, however the optimal chemotherapy regimen remains to be determined.
Objective: We report a five-year retrospective experience with preoperative Dose-Dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin (DD-MVAC) in patients with node-negative and node-positive MIBC, with a focus on the importance of the number of chemotherapy cycles.
Methods: Patients were treated between 2011 and 2015 with preoperative DD-MVAC for nodenegative or node-positive MIBC. The primary efficacy endpoint was Pathological Complete Response (pCR) on cystectomy specimens. Secondary endpoints included overall survival, relapsefree- survival and safety.
Results: Sixty-nine patients were treated with DD-MVAC, among which 14 were initially nodepositive. The median number of chemotherapy cycles was 5. Fifty-five patients underwent cystectomy, of which 52% achieved pCR. Patients who received more than 4 chemotherapy cycles achieved pCR more often although this was not statistically significant (59% versus 33%, p =0.069). There were non-significant trends toward better overall survival and relapse-free survival in patients who received more than 4 chemotherapy cycles. The cumulative incidence of grade 3-4 adverse events was 62%, mainly due to hematological toxicity. Febrile neutropenia occurred in 10% of patients. No toxic death occurred. Conclusions: DD-MVAC is an effective preoperative chemotherapy regimen for MIBC, albeit responsible for frequent but manageable hematological toxicity. Pursuing chemotherapy up to 6 cycles may result in better pathological response and better survival, although this call for confirmation by larger trials.
Bladder cancer; Neoadjuvant therapy; Cancer chemotherapy agents; Cystectomy
Dumont C, Gauthier H, Mongiat-Artus P, Daché A, Jacob F, Dadoun D, et al. Preoperative Chemotherapy with Dose-Dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin for Muscle- Invasive Urothelial Carcinoma of the Bladder. Ann Urol Res. 2018; 2(1): 1011.