Lehmann J et al. (2005) Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95). J Clin Oncol 23: 4963–4974

Lehmann et al. in Germany have published the results of a randomized, multicenter, phase III trial comparing adjuvant cisplatin plus methotrexate (CM) with methotrexate, vinblastine, epirubicin and cisplatin (MVEC) in the adjuvant treatment of patients with resected, locally advanced bladder cancer.

Half of all patients with invasive bladder cancer die if treated with radical cystectomy alone, outlining the importance of effective chemotherapy. The authors report that the gold-standard treatment is MVEC, but the severe toxicity of this regimen has prompted them to investigate less toxic alternatives.

In this study, 327 patients with stage pT3a–4a and/or pathologic node-positive transitional-cell carcinoma of the bladder were randomized to adjuvant chemotherapy with either CM (n = 163) or MVEC (n = 164). Median follow-up was 42 months. The study was designed as a noninferiority trial, and the primary endpoint was progression-free survival. The equivalence margin was set at 0.15, with the upper bound of the hazard ratio at 1.5077.

Five-year progression-free survival rates were 46.3% for the CM arm and 48.8% for the MVEC arm. Leucopenia, the most common toxic effect, was significantly higher in the MVEC arm.

The authors conclude that the CM regimen is less toxic than MVEC and cannot be considered substantially inferior in terms of efficacy. However, they also note that these results must be assessed in light of the equivalence margin of 0.15.