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. 2022 Aug;39(4):541-579.
doi: 10.1007/s10585-022-10173-8. Epub 2022 Jun 23.

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

Anne G W E Wintjens  1   2 , Geert A Simkens  3 , Peter-Paul K H Fransen  4 , Narcis Serafras  5 , Kaatje Lenaerts  6   5 , Gregor H L M Franssen  7 , Ignace H J T de Hingh  3   8 , Patricia Y W Dankers  9   10 , Nicole D Bouvy  5   8 , Andrea Peeters  11
Affiliations

Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review

Anne G W E Wintjens et al. Clin Exp Metastasis. 2022 Aug.

Abstract

For peritoneal metastases (PM), there are few curative treatment options, and they are only available for a select patient group. Recently, new therapies have been developed to deliver intraperitoneal chemotherapy for a prolonged period, suitable for a larger patient group. These drug delivery systems (DDSs) seem promising in the experimental setting. Many types of DDSs have been explored in a variety of animal models, using different cytostatics. This review aimed to provide an overview of animal studies using DDSs containing cytostatics for the treatment of gastro-intestinal PM and identify the most promising therapeutic combinations. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) guidelines. The 35 studies included revealed similar results: using a cytostatic-loaded DDS to treat PM resulted in a higher median survival time (MST) and a lower intraperitoneal tumor load compared to no treatment or treatment with a 'free' cytostatic or an unloaded DDS. In 65% of the studies, the MST was significantly longer and in 24% the tumor load was significantly lower in the animals treated with cytostatic-loaded DDS. The large variety of experimental setups made it impossible to identify the most promising DDS-cytostatic combination. In most studies, the risk of bias was unclear due to poor reporting. Future studies should focus more on improving the clinical relevance of the experiments, standardizing the experimental study setup, and improving their methodological quality and reporting.

Keywords: Animal experiments; Drug delivery systems; Intraperitoneal chemotherapy; Peritoneal metastases; Systematic review.

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Figures

Fig. 1
Fig. 1
Flow diagram of included studies
Fig. 2
Fig. 2
Overview of all included DDSs in this review
Fig. 3
Fig. 3
Risk of bias graph presented as percentage of all included studies
See this image and copyright information in PMC

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