Ravdin P M
Division of Medical Oncology, University of Texas Health Sciences Center, San Antonio, USA.
Oncology (Williston Park). 1997 Mar;11(3 Suppl 2):38-42.
The extensively studied agent docetaxel (Taxotere) has shown marked clinical activity in the treatment of anthracycline-resistant breast cancer. Phase I trials indicate that toxicities, such as mucositis and neutropenia, limit the administration of docetaxel to shorter perfusion schedules. Pharmacokinetic studies have shown that docetaxel's clearance by hepatic metabolism is correlated with a marked increase in risk of toxicity in patients with impaired liver function. Nevertheless, studies of docetaxel as front-line therapy for breast cancer were initiated because of its good activity against tumors in early studies and its close relationship to paclitaxel (Taxol), an agent with proven efficacy. Phase II studies have demonstrated excellent activity for docetaxel as a single agent, with an overall response rate of 61% in trials of a 100-mg/m2 dose. A phase III study is currently comparing docetaxel with paclitaxel as single-agent therapy. Docetaxel is expected to provide a better response rate but a higher incidence of neutropenia. The agent shows promise in adjuvant therapy, with very high response rates in anthracycline-resistant patients. Preliminary results of tests using docetaxel in combination with doxorubicin show high objective response rates but low complete response rates; early results suggest that this combination may have some advantages over paclitaxel/doxorubicin.
已被广泛研究的药物多西他赛（泰索帝）在治疗对蒽环类药物耐药的乳腺癌方面显示出显著的临床活性。I期试验表明，诸如黏膜炎和中性粒细胞减少等毒性反应限制了多西他赛采用更短灌注方案给药。药代动力学研究表明，多西他赛经肝脏代谢的清除率与肝功能受损患者毒性风险的显著增加相关。尽管如此，由于多西他赛在早期研究中对肿瘤具有良好活性且与已证实有效的药物紫杉醇（泰素）关系密切，因此启动了多西他赛作为乳腺癌一线治疗的研究。II期研究已证明多西他赛作为单一药物具有出色的活性，在100mg/m²剂量的试验中总体缓解率为61%。一项III期研究目前正在比较多西他赛与紫杉醇作为单一药物治疗的效果。预计多西他赛将提供更高的缓解率，但中性粒细胞减少的发生率更高。该药物在辅助治疗中显示出前景，在对蒽环类药物耐药的患者中缓解率非常高。使用多西他赛与阿霉素联合治疗的试验初步结果显示客观缓解率高但完全缓解率低；早期结果表明，这种联合治疗可能比紫杉醇/阿霉素具有一些优势。
