Van der Speeten Kurt, Stuart Oswald A, Sugarbaker Paul H
Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium.
Cancer J. 2009 May-Jun;15(3):216-24. doi: 10.1097/PPO.0b013e3181a58d95.
The peritoneal surface remains an important failure site for patients with gastrointestinal and gynecologic malignancies. During the last 2 decades, novel therapeutic approaches, combining cytoreductive surgery with intraoperative intracavitary and intravenous chemotherapy, have emerged for peritoneal carcinomatosis patients. This has resulted in remarkable clinical successes in contrast with prior failures. Although further clinical data from phase II and III trials supporting this combined treatment protocols are necessary, an optimalization of the wide variety of different perioperative cancer chemotherapy protocols used in these treatment regimens is equally important. To this date, a clear understanding of the pharmacology of perioperative chemotherapy is still lacking. The efficacy of intraperitoneal cancer chemotherapy protocols is governed as much by nonpharmacokinetic variables (tumor nodule size, density, vascularity, interstitial fluid pressure, and binding) as by the pharmacokinetic variables (dose, volume, duration, pressure, and carrier solution). Our recent data support the importance of the tumor nodule as the most meaningful pharmacologic end point. Timing of perioperative intravenous chemotherapy may substantially influence the pharmacokinetics. This review aims to clarify the pharmacokinetic and pharmacodynamic data currently available regarding the intraperitoneal delivery of cancer chemotherapy agents in patients with peritoneal carcinomatosis.
对于胃肠道和妇科恶性肿瘤患者而言，腹膜表面仍是一个重要的治疗失败部位。在过去20年中，针对腹膜癌患者出现了新的治疗方法，即将减瘤手术与术中腔内及静脉化疗相结合。与之前的失败情况相比，这已取得了显著的临床成功。尽管仍需要来自II期和III期试验的进一步临床数据来支持这种联合治疗方案，但优化这些治疗方案中使用的各种不同围手术期癌症化疗方案同样重要。迄今为止，对围手术期化疗的药理学仍缺乏清晰的认识。腹膜内癌症化疗方案的疗效既受非药代动力学变量（肿瘤结节大小、密度、血管分布、间质液压力和结合情况）影响，也受药代动力学变量（剂量、体积、持续时间、压力和载体溶液）影响。我们最近的数据支持将肿瘤结节作为最有意义的药理学终点的重要性。围手术期静脉化疗的时机可能会极大地影响药代动力学。本综述旨在阐明目前关于腹膜癌患者腹腔内递送癌症化疗药物的药代动力学和药效学数据。
