University Surgical Cluster, National University Health System, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Clin Cancer Res. 2021 Apr 1;27(7):1875-1881. doi: 10.1158/1078-0432.CCR-20-2152. Epub 2020 Nov 4.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m. We conducted a phase I study to establish safety and tolerability.
We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m.
This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration ( = 0.95) and AUC ( = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively.
The recommended phase II dose is 120 mg/m. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases..
加压腹腔内气溶胶化疗（PIPAC）是一种新的腹腔镜腹腔内化疗输送技术，旨在改善药物分布和组织穿透性，以治疗腹膜转移。到目前为止，PIPAC 奥沙利铂的给药剂量为 92mg/m2 任意剂量。我们进行了一项 I 期研究，以确定其安全性和耐受性。
我们对至少一线化疗失败后患有胃肠道肿瘤腹膜转移的患者使用 PIPAC 奥沙利铂的 3+3 剂量递增设计。剂量水平分别计划为 45、60、90 和 120mg/m2。
本研究共纳入 16 例患者，共进行了 24 次 PIPAC 手术（8 例胃癌；5 例结直肠癌；1 例胆囊、胰腺和阑尾癌各 1 例）。中位年龄和腹膜癌症指数（PCI）评分分别为 62 岁和 17。2 例患者在 45mg/m2 时发生胰腺炎（2 级和 3 级），需要扩大队列。另 1 例患者在 90mg/m2 时发生 2 级胰腺炎。无其他剂量限制性毒性，最高剂量组（120mg/m2）能很好地耐受 PIPAC。药代动力学分析表明，剂量与最大浓度（r=0.95）和 AUC（r=0.99）之间具有良好的线性关系。根据 RECIST，分别有 62.5%和 50%的患者在一次和两次 PIPAC 治疗后疾病稳定。共 8 例患者进行了两次 PIPAC 治疗，PCI 和腹膜消退分级评分中位数分别从 15 分降至 12 分和从 2.5 分降至 2.0 分。
推荐的 II 期剂量为 120mg/m2。未来的研究应进一步阐明 PIPAC 奥沙利铂治疗腹膜转移的疗效和作用。
