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Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes

机译:胃癌腹膜癌的突破性治疗:紫杉烷类的腹膜内化疗

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摘要

The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m2; IP PTX [without intravenous (IV) PTX], 80 mg/m2; and IP PTX (with IV PTX), 20 mg/m2. Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.
机译:化疗对胃癌腹膜癌(PC)的影响尚不清楚。最近,围手术期紫杉烷的腹膜内(IP)给药[例如紫杉醇(PTX)和多西紫杉醇(DOC)]显示出令人鼓舞的结果。在此,我们总结了将IP化疗与紫杉烷类药物一起使用的原理和方法,并回顾了临床结果。 IP施用的紫杉烷类化合物以极高的浓度在IP空间中保留48-72小时。该药物直接从表面浸润腹膜转移性结节,然后产生抗肿瘤作用,使其成为IP化疗的理想选择。紫杉烷类围手术期IP化疗有两种类型:新辅助腹膜内和全身化疗以及序贯围手术期腹膜内化疗(SPIC)。在SPIC中,患者在细胞减灭术(CRS)之后直至疾病进展之前接受新辅助IP化疗和相同的IP化疗方案。通常,在常温下,通过IP接入端口管理在常温下溶于500-1000 mL盐水中的紫杉烷类药物。根据阶段I研究,推荐剂量(RD)如下:IP DOC,45-60 mg / m 2 ; IP PTX [无静脉(IV)PTX],80 mg / m 2 ;和IP PTX(含IV PTX)为20 mg / m 2 。 II期研究报告中位生存时间为14.4-24.6 mo,1年总生存期为67%-78%。 III期研究于2011年开始,将S-1联合IP和IV PTX与S-1联合IV顺铂进行比较。接受CRS的患者的预后好于未接受CRS的患者。但是,这部分是由于选择偏见。尽管一些II期研究已显示出令人鼓舞的结果,但仍需要一项随机对照研究来验证紫杉烷类IP化疗对胃癌PC的有效性。

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