Gemcitabine and cisplatin in locally advanced and/or metastatic bladder cancer

Although transitional cell carcinoma of the urothelium is chemosensitive, long-term disease-free survival is low. Accordingly, interest has focused on combining classically active agents like cisplatin with promising new drugs. Gemcitabine has evoked interest not only because of its intrinsic activity against this cancer, but also because of its effect of inhibiting repair of DNA that has been damaged by drugs like cisplatin. Four phase II studies have assessed the effect of a gemcitabine-cisplatin combination on advanced or metastatic bladder cancer. All the studies employed a gemcitabine dose of 1000 mg/m(2) given on days 1, 8 and 15, whereas the cisplatin dose and schedule varied, with total doses ranging from 70 to 105 mg/m(2). Overall response rates in these studies ranged from 42 to 66%, with complete responses from 15 to 28%. Toxicities, which were primarily haematological, were generally manageable. This promising two-drug combination has been compared with the standard MVAC regimen (methotrexate, vinblastine, doxorubicin, and cisplatin) in a randomised phase III trial and the results are eagerly anticipated.