Escalated therapy for refractory transitional cell cancer of the bladder

Four patients with metastatic urothelial tumors refractory to standard chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) were treated with escalated dose of MVAC plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor ( rh GM-CSF ). The dose of escalated MVAC were 30mg of methotrexate/m² (Days 1. 16, 23), 4mg of vinblastine/m² (Days 1, 16, 23), 60mg of doxorubicin/m² (Day 2), and 100mg of cisplatin/m² (Day 2). In addition rhGM-CSF was adminstered at a dose of 300ug subcutaneously on days 3 to 13. Cycles were repeated every 4weeks. The patients who tolerated the first course of therapy, subsequent esclated MVAC was performed. This dose was tolerated in three patients, resulting in modest fever and hematologic toxic effect. One early death was observed. One complete response (25%) and one partial response (25%) was observed. Duration of the complete response is over 16 months and partial response is over Smonths and 2months. Although results of other investigators revealed that increasing the dose intensity of MVAC would be of limited value, escalated MVAC may be very useful selectively in refractory transitional cell cancer of the bladder.