Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models

Abstract

Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 µg/hour in vitro and 1.0 µg/hour in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3,049 ng-day/mL with the microdevice vs. 2,118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.

Improving paclitaxel pharmacokinetics by using tumor-specific mesoporous silica nanoparticles with intraperitoneal delivery

“…An implantable, nonresorbable IP micro-device was developed to release a chemotherapeutic agent to the peritoneal cavity at a constant rate. 10 Preclinical studies showed reduced toxicity by the controlled drug release from this micro-device with similar efficacy outcomes to frequent IP bolus doses. Current efforts related to IP drug delivery are mainly to provide a depot for sustained release of chemotherapeutic agents in the peritoneal tumor environment, thus increasing local drug levels while reducing systemic exposure.…”

Modelling drug transport during intraperitoneal chemotherapy

“…Additionally, the work by Colin et al [36] does estimate the changes in tumour volume based on a PDPD link suggested by Ait-Oudhia et al [65]. Given the recent interest in metronomic chemotherapy in the context of IP chemotherapy [66], extending models to include growth and cell survival might become more frequent.…”

Enhancing Delivery of Small‐Molecule‐ and Cell‐Based Therapies for Ovarian Cancer Using Advanced Delivery Strategies

“…who developed a delivery device for IP administration of cisplatin. [ 155 ] The device design was based on in vitro work by the group that demonstrated that sustained low doses of cisplatin produced better killing of ovarian cancer cells than intermittent dosing. [ 156 ] The devices used were fabricated from poly‐ l ‐lactic acid and consisted of a spherical chamber and cap.…”

“…The cap had a circular orifice with a diameter of 180 μm, chosen to control cisplatin release based on its solubility and diffusivity. [ 155 ] The devices were loaded with 5 mg cisplatin powder. The device was tested in mice, using weekly IP bolus injections (5 mg kg −1 ) as a control.…”

“…The device released cisplatin continuously over 42 days with an approximate release rate of 1 μg h −1 . [ 155 ] Both IP injection and cisplatin delivery using the device significantly reduced tumor burden compared to the untreated control. There was no significant difference in tumor mass or tumor burden between the IP bolus injection and microdevice groups.…”