Phase I study of intraperitoneal irinotecan with systemic capecitabine and oxaliplatin for patients with gastric peritoneal metastases.

Background: Peritoneal metastases of gastric cancer are associated with a poor prognosis (median overall survival (OS) ∼9 months). Catheter-based intraperitoneal (CBIP) chemotherapy is a locoregional approach to deliver chemotherapy leading to higher intraperitoneal (IP) concentrations of cytotoxic drugs compared to intravenous administration.

Method: This multicenter, open-label 3 + 3 + 3 dose-escalation phase I trial evaluated 3-weekly IP irinotecan with oral capecitabine and intravenous oxaliplatin (CAPOX).

A Clinical Pharmacological Perspective on Intraperitoneal Chemotherapy.

Peritoneal metastases (PM), frequently observed in malignancies such as ovarian, colorectal, pancreatic, and gastric cancers, present a significant therapeutic challenge due to poor prognosis and limited effectiveness to systemic chemotherapy. The peritoneal-plasma barrier reduces effective drug transfer from plasma to the peritoneal cavity, reducing cytotoxic effects on PM. Intraperitoneal (IP) chemotherapy offers a locoregional approach, enabling high local drug concentrations that can enhance therapeutic efficacy while limiting systemic toxicity.

Pharmacokinetic boosting of olaparib: Study protocol of a multicentre, open-label, randomised, non-inferiority trial (PROACTIVE-B).

Background: Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of the anticancer drug olaparib, a CYP3A-substrate, has the potential to reduce PK variability, side effects and financial burden associated with this drug. After establishing adequate pharmacokinetic exposure with boosting in the PROACTIVE-A study, the PROACTIVE-B study is designed to evaluate non-inferiority for both efficacy and toxicity of the boosted therapy compared to the standard monotherapy of olaparib.

The prognostic value of peritoneal metastases in patients with gastric cancer: a nationwide population-based study.

Background: The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer.