Results from a randomized controlled trial that compared MVAC with docetaxel plus cisplatin in 220 patients reported that MVAC was associated with longer OS (median survival, 14.2 months vs. 9.3 months; P = .026).
A randomized trial that compared MVAC with cisplatin, cyclophosphamide, and doxorubicin demonstrated improved response and median survival rates (48 weeks vs. 36 weeks; P = .003) with the MVAC regimen.
Results from a randomized trial that compared MVAC with single-agent cisplatin in advanced bladder cancer also showed a significant advantage with MVAC in both response rate and median survival (12.5 months vs. 8.2 months; P = .002).
A multicenter randomized controlled trial compared CMV with methotrexate plus vinblastine without cisplatin in 214 patients. The relative risk of dying was 0.68 (95% confidence interval [CI], 0.51–0.90; P = .0065) in favor of CMV. The median survival was 7 months with CMV and 4.5 months with methotrexate plus cisplatin.
The European Organisation for Research and Treatment of Cancer (EORTC) conducted another randomized trial that studied 263 patients with advanced bladder cancer and evaluated the efficacy of a high-dose intensity MVAC regimen administered every 2 weeks with granulocyte colony-stimulating factor (G-CSF) versus a classic MVAC regimen administered every 4 weeks.
Although there was no significant difference in OS at a median follow-up of 3.2 years (hazard ratio [HR], 0.80; 95% CI, 0.60–1.06; P = .122), an update at a median follow-up of 7.3 years reported that the high-dose intensity MVAC regimen was associated with improved OS (HR, 0.76; 95% CI, 0.58–0.99; P = .042), with a 5-year survival rate of 22% compared with 14% in patients treated with the classic MVAC regimen.
The high-dose intensity MVAC regimen was also associated with higher response rates (72% vs. 58%; P = .016), improved median progression-free survival (9.5 months vs. 8.1 months; P = .017), and decreased neutropenic fever (10% vs. 26%; P < .001), although only 19% of patients treated with a classic MVAC regimen ever received G-CSF.[Level of evidence: 1iiA] An imbalance in baseline prognostic factors (i.e., visceral metastases were found in 37 patients randomly assigned to the high-dose MVAC regimen and 47 patients assigned to the classic MVAC regimen) may account, in part, for these results.
Gemcitabine plus cisplatin.
In a multicenter randomized phase III trial that compared GC with the MVAC regimen in 405 patients with advanced or metastatic bladder cancer, GC yielded response rates, time-to-progression, and OS (HR, 1.04; 95% CI, 0.82–1.32; P = .75) similar to MVAC, but GC had a better safety profile and was better tolerated than MVAC.
Although this study was not designed to show the equivalence of the two regimens, the similar efficacy and reduced toxic effects of GC make it a reasonable alternative in patients who may not tolerate the MVAC regimen.[Level of evidence: 1iiA]