Gemcitabine in advanced bladder cancer

The methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) regimen has been considered standard therapy for advanced bladder cancer. However, the toxicity of this regimen motivated the development of safer and/or more effective therapy. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) is a promising new agent with activity in advanced disease. Early phase studies yielded response rates of 23% to 29% with single-agent treatment and 41% to 57% with the combination of gemcitabine/cisplatin (GC). In a randomized phase III trial involving 405 randomized patients with locally advanced or metastatic bladder cancer, data comparing gemcitabine at 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin at 70 mg/m(2) on day 2 every 28 days with standard MVAC demonstrated that the two regimens were associated with comparable response rates, time to disease progression, and overall survival. The GC regimen was associated with superior safety and tolerability, including reduced frequencies of grade 3/4 mucositis (1% v 22%), neutropenic fever (2% v 14%), and neutropenic sepsis (1% v 12%). These findings suggested that on the basis of superior risk to benefit ratio, the GC regimen should be favored as standard treatment in advanced bladder cancer. Other promising combinations include gemcitabine/cisplatin/paclitaxel, and a phase III trial comparing this triple-agent combination with the GC regimen in advanced bladder cancer patients has been initiated. Semin Oncol 28 (suppl 7):11-14.