Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal administration of antineoplastic agents

Antineoplastic agents are currently being administered through catheters placed intraperitoneally to treat cancer localized to the peritoneum. This route allows for high local concentrations of antineoplastic drug at the tumor site with low levels of the drug systemically, thereby reducing the systemic toxicity. However, there are complications with this mode of delivery, including a decrease in catheter patency and induction of adhesion formation, which leads to decreased drug dispersion and limits continuing drug administration. A model was developed in rats to mimic this method of antineoplastic drug administration that produced fibrin deposition around the catheter and adhesion formation involving bowel, intestines and liver. All antineoplastic agents tested, including Adriamycin, methotrexate, bleomycin, mitoxantrone and cisplatin, induced moderate to severe adhesion formation with varying effects on catheter patency. When an intraperitoneal bolus of tometin encapsulated in liposomes was tested with Adriamycin delivered via an osmotic minipump, a reduction in adhesion formation was observed. However, highly significant adhesion reduction was found when tolmetin was coadministered with the antitumor agents.