Koemans W J, van der Kaaij R T, Wassenaar E C E, Grootscholten C, Boot H, Boerma D, Los M, Imhof O, Schellens J H M, Rosing H, Huitema A D R, van Sandick J W
Department of Surgical Oncology, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Departments of Surgery, Sint Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands.
Eur J Surg Oncol. 2021 Feb;47(2):486-489. doi: 10.1016/j.ejso.2020.07.037. Epub 2020 Aug 5.
In the PERISCOPE I study, gastric cancer patients with limited peritoneal dissemination were treated with systemic chemotherapy followed by (sub)total gastrectomy, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with 460 mg/m hyperthermic oxaliplatin followed by normothermic docetaxel in escalating doses (0, 50, 75 mg/m). In total, 25 patients completed the study protocol. Plasma samples were collected before the start of the HIPEC procedure, after oxaliplatin washing, after docetaxel washing and the following morning. Median peak plasma concentrations were 5.5∗10 mg/ml for oxaliplatin, 89∗10 mg/ml for docetaxel (dose 50 mg/m) and 113∗10 mg/ml for docetacel (dose 75 mg/m2). The following morning median plasma concentrations were 32% and 4% of the measured peak concentrations for oxaliplatin and docetaxel, respectively. For both cytostatic agents, no correlation was found between intraperitoneal fluid concentration and peak plasma concentration. High doses oxaliplatin and docetaxel can be given intraperitoneally without causing potentially toxic systemic concentrations.
在“潜望镜”研究中,对腹膜播散受限的胃癌患者先进行全身化疗,然后进行(次)全胃切除术、细胞减灭术和腹腔内热化疗(HIPEC),使用460mg/m²的热奥沙利铂,随后给予递增剂量(0、50、75mg/m²)的常温多西他赛。共有25例患者完成了研究方案。在HIPEC手术开始前、奥沙利铂冲洗后、多西他赛冲洗后以及次日早晨采集血浆样本。奥沙利铂的血浆峰值浓度中位数为5.5×10mg/ml,多西他赛(剂量50mg/m²)为89×10mg/ml,多西他赛(剂量75mg/m²)为113×10mg/ml。次日早晨,奥沙利铂和多西他赛的血浆浓度中位数分别为所测峰值浓度的32%和4%。对于这两种细胞毒性药物,未发现腹腔内液体浓度与血浆峰值浓度之间存在相关性。高剂量的奥沙利铂和多西他赛可经腹腔给药,而不会导致潜在的全身中毒浓度。