THE ROLE OF PACLITAXEL IN CHEMOSENSITIVE UROLOGICAL MALIGNANCIES - CURRENT STRATEGIES IN BLADDER-CANCER AND TESTICULAR GERM-CELL TUMORS

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, pacl itaxel is one of the most active drugs in metastatic bladder cancer. O ngoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ong oing clinical trials focus on the combination of paclitaxel with cispl atin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxe l administration has been demonstrated to be easily applicable to pati ents with reduced renal function, requiring no dose reduction and prod ucing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (m ethotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally , the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involvi ng a total of 83 patients a response rate of 26% has been observed usi ng dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m(2). The major toxicities of paclitaxel include n eutropenia, neurotoxicity, and fatigue syndrome. Currently, combinatio ns of paclitaxel with cisplatin +/- ifosfamide are used as first- or s econd-line salvage therapy in patients with relapsed metastatic testic ular cancer. The German Testicular Cancer Study Group uses a paclitaxe l (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage t reatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemoth erapy with PBSC rescue. Since only a few drugs have demonstrated subst antial activity in cisplatin-refractory disease, paclitaxel will be us ed in early salvage strategies and, possibly, as first-line chemothera py as a part of platinum-based combination regimens in patients with t esticular cancer. Further trials confirming the important role of pacl itaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.