Dataset Information

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

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).

SUBMITTER: Ceelen W

PROVIDER: S-EPMC9297106 | biostudies-literature |

REPOSITORIES: biostudies-literature

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