Bokemeyer C, Hartmann J T, Kuczyk M A, Truss M C, Beyer J, Jonas U, Kanz L
Abteilung für Hämatologie/Onkologie/Rheumatologie/Immunologie, Eberhard-Karls-Universität Tübingen, Germany.
World J Urol. 1996;14(6):354-9. doi: 10.1007/BF00183114.
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, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing 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. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, 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 involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. 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 chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.
近期研究结果表明，紫杉醇在尿路上皮癌患者和睾丸癌患者中发挥着越来越重要的作用。作为单一药物，紫杉醇的缓解率在40%-50%之间，是转移性膀胱癌中活性最高的药物之一。正在进行的紫杉醇与顺铂或顺铂和异环磷酰胺联合化疗试验显示，客观缓解率大幅高于70%，此外，完全缓解率也很高。因此，紫杉醇作为转移性膀胱癌一线联合化疗的一部分时，似乎是一种重要药物。正在进行的临床试验聚焦于紫杉醇与顺铂、异环磷酰胺、吉西他滨和卡铂的联合应用。此外，已证明紫杉醇给药很容易应用于肾功能减退的患者，无需降低剂量，且不会增加毒性。未来的策略将不得不比较最有效的紫杉醇联合方案与一线MVAC（甲氨蝶呤、长春碱、阿霉素、顺铂）化疗。最后，需要探索紫杉醇联合方案在膀胱癌患者辅助和新辅助治疗中的作用。在睾丸癌中，紫杉醇最初是在顺铂难治性疾病患者中进行试验的。在总共涉及83例患者的4项连续试验中，观察到采用3小时至24小时输注以及175至250mg/m²剂量的给药方案时，缓解率为26%。紫杉醇的主要毒性包括中性粒细胞减少、神经毒性和疲劳综合征。目前，紫杉醇与顺铂+/-异环磷酰胺的联合方案被用作复发性转移性睾丸癌患者的一线或二线挽救治疗。德国睾丸癌研究组使用紫杉醇（泰素、异环磷酰胺、顺铂；TIP）联合方案作为挽救治疗。遵循TIP方案并应用粒细胞集落刺激因子（G-CSF）后，采集外周血干细胞（PBSC），随后患者接受高剂量化疗并进行PBSC救援。由于只有少数药物在顺铂难治性疾病中显示出显著活性，紫杉醇将用于早期挽救策略，并且可能作为睾丸癌患者基于铂类联合方案一部分的一线化疗。进一步试验证实紫杉醇在这种高度可治愈的恶性肿瘤中的重要作用，并对其急性和长期毒性进行全面研究将是未来的任务。
