Tissue levels of cisplatin in previously traumatized tissue without adhesion formation in a rabbit sidewall adhesion and intraperitoneal delivery model

Abstract

5525 Background: It has been hypothesized that the presence of extensive adhesions after ovarian cancer resection may limit the distribution of intraperitoneal (IP) chemotherapeutics. The objective of this study was to determine if using a hyaluronate/carboxymethylcellulose (HA/CMC) barrier to prevent adhesions during a simulated tumor resection surgery would increase tissue drug levels following subsequent IP chemotherapy. Methods: A sidewall defect/cecal abrasion model was used to induce adhesion formation and simulate tumor resection trauma in 22 rabbits. Seven rabbits received HA/CMC at the end of the surgery. Four weeks after surgery, cisplatin (2.5mg/kg) was administered IP to HA/CMC treated and untreated animals or IV to untreated controls. Animals were sacrificed 24hrs after infusion and tissue samples were collected from inside the defect (with or without adhesions) and outside the defect on the contralateral sidewall. Samples were cryosectioned and analyzed for platinum content by ICP/MS. Results: Platinum tissue levels in the uppermost peritoneal layer (0–1mm) were significantly higher for IP delivery than IV and were the highest for IP delivery when no adhesions were present inside the defect. Platinum levels were significantly higher in the previously traumatized tissue inside the defect than in untraumatized tissue outside the defect. This was consistent for both IP or IV and HA/CMC treated or untreated animals. The benefit of HA/CMC was underscored by the fact that samples under adhesions could not be obtained for that group due to the significant reduction in adhesion formation compared to untreated controls. Conclusions: Recently traumatized tissue without adhesions had the highest platinum levels following IP cisplatin in this model. The previously traumatized tissue had significantly higher platinum levels than untraumatized tissue likely due to both increased peritoneal diffusion and systemic delivery components. [Table: see text] [Table: see text]