Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases

EBioMedicine. 2022 Aug;82:104151. doi: 10.1016/j.ebiom.2022.104151. Epub 2022 Jul 15.

Abstract

Background: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a novel method to treat patients with peritoneal metastases (PM). We aimed to study the tolerability, safety, pharmacokinetics, and tumour response of nanoparticle albumin bound paclitaxel (NAB-PTX) during PIPAC in a Phase I study.

Methods: Eligible patients with biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin underwent three PIPAC treatments using NAB-PTX with a four-week interval. The dose of NAB-PTX was escalated from 35 to 140 mg/m2 using a Bayesian design to estimate the maximum tolerated dose (MTD).

Findings: Twenty-three patients were included; thirteen (65%) patients combined PIPAC therapy with continued systemic chemotherapy. The most frequent toxicities were liver toxicity and anaemia. Treatment resulted in seven (35%) responders, six (30%) non-responders and seven (35%) patients with stable PM. Systemic absorption of NAB-PTX was slow, with median peak plasma concentrations reached after 3 to 4 h. Median NAB-PTX tumour tissue concentrations suggested accumulation: 14.6 ng/mg, 19.2 ng/mg and 40.8 ng/mg after the first, second and third PIPAC procedure respectively. EORTC QoL and VAS scores remained stable. Overall survival after one year was 57%.

Interpretation: PIPAC with NAB-PTX results in a favourable PK profile and promising anticancer activity in patients with unresectable PM. The MTD and recommended Phase II clinical trial dose are 140 mg/m2. In patients with impaired hepatobiliary function, a dose of 112.5 mg/m2 is recommended.

Funding: Kom op tegen Kanker (Flemish League against Cancer).

Keywords: Nanoparticle; PIPAC; Paclitaxel; Peritoneal carcinomatosis; Peritoneal metastases.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Albumins* / toxicity
  • Antineoplastic Combined Chemotherapy Protocols
  • Bayes Theorem
  • Humans
  • Nanoparticles* / toxicity
  • Paclitaxel* / toxicity
  • Peritoneal Neoplasms* / drug therapy
  • Peritoneal Neoplasms* / secondary
  • Quality of Life

Substances

  • Albumins
  • Paclitaxel