Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA.
Gynecol Oncol. 2018 Dec;151(3):555-561. doi: 10.1016/j.ygyno.2018.09.007. Epub 2018 Sep 22.
The peritoneal spread of ovarian cancer makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Intraperitoneal delivery exposes the tumor to concentrations of cytotoxic drugs much greater than with intravenous delivery, and in vitro studies have also shown that combining hyperthermia and platinum leads to an additive cytotoxic effect. Pharmacokinetic analyses have confirmed very high concentrations of cytotoxic drugs in the peritoneal cavity, with minimal systemic exposure and toxicity. The majority of historical data evaluating HIPEC in ovarian cancer are based on retrospective research, which included heterogeneous groups of patients and drugs used for HIPEC. Recent publications on the findings of prospective studies, including the first randomized trial in which the only difference in intervention was the addition of HIPEC with cisplatin to interval debulking surgery in stage III patients, have shown a benefit in favor of HIPEC. Yet, a recent prospective study from Korea did not find a benefit. Opponents of HIPEC have cited higher rates of complications with this approach, yet most of the serious adverse events observed are likely related to the surgery itself, and are comparable to the rates reported in studies evaluating cytoreductive surgery without HIPEC. Findings from a recent randomized controlled trial showed no delays in initiation or completion of postoperative chemotherapy in patients treated with HIPEC. A growing body of evidence is indicating that it might be time to seriously consider HIPEC as a complementary treatment at the time of cytoreductive surgery for patients with advanced-stage ovarian cancer in the setting of an experienced center. Yet, more research is needed to identify the population of patients who gain the most benefit from this therapy.
腹腔内播散使卵巢癌成为高热腹腔内化疗(HIPEC)的潜在靶点。腹腔内给药使肿瘤暴露于细胞毒性药物的浓度远高于静脉内给药,体外研究还表明,将热疗和铂类药物联合使用可产生附加的细胞毒性作用。药代动力学分析证实腹腔内存在非常高浓度的细胞毒性药物,而全身暴露和毒性最小。评估卵巢癌中 HIPEC 的大多数历史数据基于回顾性研究,这些研究包括异质性的患者群体和用于 HIPEC 的药物。最近关于前瞻性研究结果的出版物,包括首例随机试验,其中干预的唯一区别是在 III 期患者的间隔减瘤手术中添加顺铂的 HIPEC,表明 HIPEC 有利。然而,最近来自韩国的一项前瞻性研究并未发现获益。HIPEC 的反对者引用了这种方法更高的并发症发生率,但大多数观察到的严重不良事件可能与手术本身有关,与评估无 HIPEC 的细胞减灭术的研究报告的发生率相当。最近一项随机对照试验的结果表明,接受 HIPEC 治疗的患者在接受手术后化疗的开始或完成方面没有延迟。越来越多的证据表明,在有经验的中心,对于晚期卵巢癌患者,在进行细胞减灭术时,HIPEC 作为一种补充治疗可能是时候认真考虑了。然而,还需要更多的研究来确定从这种治疗中获益最多的患者群体。