SWOG 8710 (INT-0080): Randomized Phase III Trial of Neoadjuvant MVAC+Cystectomy Versus Cystectomy Alone in Patients With Locally Advanced Bladder Cancer
James Metz, MD
University of Pennsylvania Cancer
Last Modified: May 14, 2001
Presenter: R.B. Natale Affiliation: SWOG
Radical cystectomy has been the gold standard for the treatment of locally advanced bladder cancer. However, 50-60% develop recurrent or metastatic disease after cystectomy. It has been hypothesized that neoadjuvant therapy for advanced bladder cancer will 1)immediately treat micrometastatic disease, 2) downstage tumors and improve efficacy of surgery, and 3)allow better tolerance and compliance to chemotherapy when compared to adjuvant chemotherapy. This trial was designed to test MVAC in the neoadjuvant setting.
Materials and Methods:
317 patients with T2-4N0M0 transitional cell carcinoma of the bladder were enrolled over a period of 12 years
Patients were randomized to cystectomy alone (arm 1) vs 3 cycles of MVAC prior to cystectomy (arm 2)
Arm 2 had a 33% incidence of grade IV granulocytopenia and 29% incidence of GI complications
82% underwent the planned cystectomy in each arm
There was no difference in the post-cystectomy complication rates
5 yr overall survival was 57% vs 42% favoring the MVAC arm (p<0.044, 1 sided t-test)
Patients with a pathologic complete response had an overall survival of 85% at 5 years
MVAC is safe prior to radical cystectomy, although toxicity can be moderately severe
MVAC does not decrease the chances of a patient having a radical cystectomy
This is the first randomized trial to show both a clinically and statistically significant advantage to the addition of neoadjuvant chemotherapy in locally advanced bladder cancer
Neoadjuvant MVAC can be offered as a treatment option
A confirmatory trial is needed to support these results
This is a controversial trial for a number of reasons. It accrued patients over a long period of time(12 years) which questions the selection of patients for this trial and the broad applicability to patients. There is significant controversy regarding the choice of statistical analysis of using a one sided t-test. If a 2 sided t-test was used, this trial would not be statistically significant. Seven previous randomized trials of neoadjuvant chemotherapy for advanced bladder cancer have been negative. Although neoadjuvant therapy with MVAC is an option, it should not be considered the standard of care until a confirmatory trial is performed.
Feb 10, 2011 - The results of two phase 3, randomized controlled trials suggest that two therapies, sunitinib and everolimus, hold promise in the treatment of patients with advanced pancreatic neuroendocrine tumors; the findings of these trials have been published in the Feb. 10 issue of the New England Journal of Medicine.