de Bree E, Rosing H, Michalakis J, Romanos J, Relakis K, Theodoropoulos P A, Beijnen J H, Georgoulias V, Tsiftsis D D
Department of Surgical Oncology, Medical School of Crete University Hospital, Herakleion, Greece.
Eur J Surg Oncol. 2006 Aug;32(6):666-70. doi: 10.1016/j.ejso.2006.03.008. Epub 2006 Apr 17.
Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.
紫杉醇和多西他赛是目前临床上可用的两种紫杉烷类药物。紫杉烷类药物与铂类化合物的联合应用已成为原发性卵巢癌全身化疗的首选方案。尽管这些药物在全身化疗中具有较高的活性,但大多数晚期卵巢癌患者仍会复发,最终死于该疾病。因此,需要更有效的全身化疗方案或替代治疗方式。腹腔内化疗就是这样一种替代治疗选择。关于腹腔内给予紫杉醇和多西他赛的药代动力学研究表明,局部药物浓度和暴露量非常高。它们的活性和反应似乎呈剂量依赖性,因此预期在全身毒性有限的情况下具有更高的疗效。腹腔内化疗可在术中与热疗联合应用,热疗可增强许多药物的组织穿透力和细胞毒性活性。关于紫杉烷类药物热增强作用的数据并不一致,但在腹腔内给药提供的高局部浓度下,这种热增强作用似乎是存在的。临床研究已明确证实,在卵巢癌患者中进行紫杉烷类药物腹腔内灌注化疗具有可行性和有效性。一项III期研究的初步结果表明,在最佳原发性细胞减灭术后,在全身化疗基础上加用腹腔内灌注化疗可改善预后。一项单独的研究中进行了多西他赛术中热腹腔内化疗,并观察到了有前景的结果。需要进一步进行有足够随访期的临床研究,以证实这些有前景的初步结果,并确定这些药物腹腔内化疗的确切疗效。