Safety and efficacy of cisplatin and nab-paclitaxel pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal carcinomatosis: Nab-PIPAC phase 1b study.

IF 11.2 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2026-10-01 Epub Date: 2026-09-11 DOI:10.1016/j.ebiom.2026.106477

Manuela Undurraga, Noemie Lang, Thibaud Koessler, Antonella Diciolla, Mariagrazia Di Marco, Nicolas Mach, Catherine Raimond, Vassilis Genoud, Valentine Du Bois, Jean-Christophe Tille, Aurelie Bornand, Jonathan S Moore, Marc Weiner, Laure Smekens, José L Sandoval, Julie Terzic, Yann Christinat, Jennifer Veillard, Petros Tsantoulis, Paul Thoueille, Thomas Mercier, Stefan Monig, Patrick Petignat, Christian Toso, Laurent Decosterd, Martin Hübner, Intidhar Labidi-Galy, Frederic Ris

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引用次数: 0

Abstract

Background: Platinum and taxanes are backbone chemotherapy in multiple solid tumours. We aimed to investigate the safety, tolerability, and pharmacokinetics of nab-paclitaxel and cisplatin administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC).

Methods: Nab-PIPAC is a phase 1b trial investigating PIPAC administration of cisplatin at 10.5 mg/m² and escalating dose of nab-paclitaxel with a 3 + 3 design (7.5, 15, 25, 37.5, 52.5 and 70 mg/m²). PIPAC was repeated at 4-6 weeks intervals for up to three courses to estimate the maximum tolerated dose (MTD).

Findings: We enrolled 22 patients with peritoneal carcinomatosis, of whom 18 received at least one PIPAC: 6 ovarian, 9 gastric and 3 pancreatic cancers. Four patients (ovarian cancer) did not receive PIPAC due to bowel obstruction (n = 1) or no access to peritoneal cavity (n = 3). Median age was 67 years (43-81). In total, 45 PIPAC procedures were administered and 12 of 18 (67%) patients completed three PIPAC cycles. There was no dose limiting toxicity. The most common side effect was abdominal pain. One patient had grade 3 treatment related adverse event: bladder lesion requiring surgical reintervention. Median progression-free survival was 3.5 months and median overall survival was 9.4 months. Five patients with gastrointestinal cancer survived more than one year (3 gastric and 2 pancreatic). Pharmacokinetic analyses showed good linearity between nab-paclitaxel dose and the AUC_0-last (R² = 0.90).

Interpretation: The combination of nab-paclitaxel and cisplatin administered by PIPAC was safe and well tolerated in patients with peritoneal carcinomatosis. Further investigation of this combination is warranted.

Funding: The study was supported by la bourse jeune chercheur des Hopitaux Universitaires de Geneve (NL), Fondation Fond'action (ILG) and Fondation NOVA (ILG).

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顺铂和nab-紫杉醇加压腹腔喷雾化疗（PIPAC）在腹膜癌患者中的安全性和有效性：Nab-PIPAC 1b期研究

背景：铂类和紫杉烷类是多发性实体瘤的主要化疗药物。我们的目的是研究nab-紫杉醇和顺铂联合加压腹腔喷雾化疗（PIPAC）的安全性、耐受性和药代动力学。方法：Nab-PIPAC是一项1b期临床试验，采用3 + 3设计（7.5、15、25、37.5、52.5和70 mg/m2），研究了顺铂10.5 mg/m2和nab-紫杉醇剂量递增的PIPAC给药。PIPAC每隔4-6周重复3个疗程，以估计最大耐受剂量（MTD）。结果：我们纳入了22例腹膜癌患者，其中18例接受了至少一种PIPAC: 6例卵巢癌，9例胃癌和3例胰腺癌。4例（卵巢癌）患者因肠梗阻（n = 1）或无法进入腹腔（n = 3）而未接受PIPAC治疗。中位年龄为67岁（43-81岁）。总共进行了45次PIPAC手术，18例患者中有12例（67%）完成了3个PIPAC周期。没有剂量限制毒性。最常见的副作用是腹痛。1例患者有3级治疗相关不良事件：膀胱病变需要手术再干预。中位无进展生存期为3.5个月，中位总生存期为9.4个月。5例胃肠癌患者存活1年以上（3例胃癌，2例胰腺癌）。药代动力学分析显示，nab-紫杉醇剂量与AUC0-last呈良好的线性关系（R2 = 0.90）。结论：PIPAC联合nab-紫杉醇和顺铂治疗腹膜癌患者安全且耐受性良好。有必要对这种组合进行进一步调查。资助：本研究得到了日内瓦大学高等教育学院（NL）、慈善行动基金会（ILG）和NOVA基金会（ILG）的支持。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.