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Neoadjuvant Dose-Dense Methotrexate, Vincristine, Adriamycin, Cisplatin (dd-MVAC) in Patients With Muscle Invasive Bladder Cancer
Stephen B. Williams, M.D., Anne K. Mongiu, M.D., Ph.D., Fabio A. Schutz, M.D., Michelle S. Hirsch, M.D., Ph.D., Nikhil H. Ramaiya, M.B.B.S., Graeme S. Steele, M.D., Jim C. Hu, M.D., M.P.H., Toni K. Choueiri, M.D., Jonathan E. Rosenberg, M.D..
Brigham and Women's Hospital, Boston, MA, USA.

Background:
In advanced bladder cancer, administering dose-dense Methotrexate, Vincristine, Adriamycin, Cisplatin (dd-MVAC) in comparison to conventional MVAC results in less toxicity, fewer dose delays, and delivery in half the time when used with G-CSF. We retrospectively evaluated whether the use of dose-dense neoadjuvant chemotherapy followed by radical cystectomy (RC) for patients with muscle invasive T2-T4a N0-2 disease without distant metastases bladder cancer influenced the likelihood of downstaging, perioperative complications, cancer-specific and overall survival.
Methods:
Patients with clinical stage T2-T4a, N0-2, M0 bladder cancer receiving neoadjuvant dose-dense methotrexate, vinblastine, adriamycin, cisplatin chemotherapy (dd-MVAC) followed by RC at Dana Farber/Brigham and Women’s Cancer Center from January 2006 to January 2010 were identified and clinical data reviewed.
Results:
A total of 166 patients who underwent RC were identified. Of these, 10 (6%) patients underwent neoadjuvant dd-MVAC followed by RC. Median follow-up time was 11.3 months. Clinical stage at the time of diagnosis was T3 in 7 (70%) and T4a in 3 (30%) with 4 (40%) patients having radiographic nodal involvement. The median time interval from start of chemotherapy to RC was 91 days (IQR, 78-174 days). Radiologic and pathologic responses were noted in 9 (90%) and 7 (70%) patients, respectively. Of the 6 cases with microscopic residual tumor, 3 contained only carcinoma in-situ, and 3 contained small nests and individual carcinoma cells that extended into the muscularis propria. Overall, seven (70%) patients had chemotherapy related adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) including three (30%) grade 1-2 and 4 (40%) grade 3 adverse events. All patients who underwent dd-MVAC underwent cystectomy. There was one death which occurred 1.4 years after surgery.
Conclusions:
Men undergoing dose-dense neoadjuvant chemotherapy followed by RC resulted in radiographic and pathologic responses for the majority of cases. These data support the current phase II trials currently underway which are needed to delineate whether this neoadjuvant chemotherapy regimen is effective in patients with muscle invasive disease.


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