Lay Summary: Chemotherapy agents that have shown activity in metastatic bladder cancer include paclitaxel, docetaxel, ifosfamide, gallium nitrate, and gemcitabine.
A prospective, randomized trial of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) compared with cisplatin, cyclophosphamide, and doxorubicin demonstrated improved response and median survival rates (48 weeks vs. 36 weeks, P = .0003) with the former regimen. Results from a randomized trial that compared M-VAC with single-agent cisplatin in advanced bladder cancer also showed a significant advantage with M-VAC in both response rate and median survival (12.5 months vs. 8.2 months, P = .0002). The (outpatient) regimen of paclitaxel and carboplatin achieved response rates in the range of 50% in single-institution phase II trials. [Level of evidence: 3iiiDiii] However, when this regimen was evaluated in a multicenter phase II study conducted by the Southwest Oncology Group, the response rate was only 21%. Gemcitabine has shown activity in phase II trials of patients with metastatic bladder cancer. In a multicenter, randomized, phase III trial comparing the combination of gemcitabine/cisplatin (GC) with the M-VAC regimen in 405 patients with advanced or metastatic bladder cancer, GC yielded similar response rates, time-to-progression, and overall survival (hazard ratio [HR] = 1.04; 95% confidence interval [CI], 0.82-1.32; P = .75) compared with M-VAC, but GC had a better safety profile and was better tolerated than M-VAC. Although this study was not designed to show the equivalence of the 2 regimens, the similar efficacy and reduced toxic effects of GC make it a reasonable alternative in patients who may not tolerate the M-VAC regimen. Another regimen that compares in effectiveness is cispatin/methotrexate/vinblastine.
The regimen of cisplatin/gemcitabine/paclitaxel is in an active phase II trial. As such it is considered by the plan to be investigtional/experimental. It is not standard of care.
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