Overview of bladder cancer trials in the European Organization for Research and Treatment

In the 1990s, the European Organization for Research and Treatment of Cancer Genito-Urinary (EORTC GU) Group focused on dose-intensity concepts of the methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimen for patents with bladder cancer. In a randomized trial in patients with advanced urothelial cell cancer, standard MVAC was compared with 2-weekly intensified MVAC plus granulocyte-colony stimulating factor (G-CSF) support. Although the dose-intensified therapy resulted in a higher overall and complete response rates, it did not result in a better median survival. In parallel, the Spanish Oncology Genitourinary Group (SOGUG), in collaboration with the EORTC GU Group, conducted Phase I and 11 trials to investigate the feasibility and efficacy of the incorporation of two new active agents, gemcitabine and paclitaxel, into two-drug or three-drug cisplatin-based or carboplatin-based regimens. The EORTC GU Group currently is conducting randomized studies of combined paclitaxel, cisplatin, and gemcitabine compared with combined gemcitabine plus cisplatin in patients with good performance status and good renal function and studies of combined gemcitabine plus carboplatin compared with combined carboplatin, methotrexate, and vinblastine in patients who are unsuited for cisplatin. In the 1990s, the EORTC coordinated a large Intergroup study of neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy versus no chemotherapy before definitive treatment. That study included 976 patients and was based on a design to detect at least a 10% absolute improvement in survival. The final results showed a 5.5% survival difference at 3 years in the chemotherapy arm. The EORTC GU Group currently is coordinating an Intergroup study that was designed to detect an improvement of 7% in absolute survival in the adjuvant setting. (C) 2003 American Cancer Society.