[Gemcitabine and urothelial tumours]

Since 1985, standard chemotherapy of metastatic urothelial tumours has been based on a combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC protocol). Two major lessons have been learned from the use of M-VAC, namely, clear evidence of chemo-sensitivity, and an absence of chemo-curability associated with notable toxicity. Three phase II studies using gemcitabine monotherapy have demonstrated promising efficacy with an objective response rate of 22-28%, and a satisfactory toxicity profile. Three further phase II studies have confirmed the efficacy of gemcitabine in association with cisplatine (GC protocol), with a response rate of 42-66%, of which 18-28% were complete responses. The main adverse effects were haematological, including neutropenia, or grade 3 or 4 thrombocytopenia without any symptoms of fever or significant haemorrhage. Current research with gemcitabine in the treatment of urothelial tumours is aimed at optimising administration of the GC protocol, investigating the use of gemcitabine in association with other cytotoxic agents such as taxanes, or expanding the use of this drug as adjuvant therapy. The results of a phase III study to compare the efficacy and toxicity of the M-VAC and GC protocols are eagerly awaited.