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

Abstract

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