Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models
Author(s)Na, Young Jeong; Fulci, Giulia; del Carmen, Marcela G.; Birrer, Michael J.; Ye, Hongye; Tanenbaum, Laura Melanie; Mantzavinou, Aikaterini; Cima, Michael J.; ... Show more Show less
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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/h in vitro and 1.0 μg/h 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 3049 ng day/mL with the microdevice vs. 2118 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.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Koch Institute for Integrative Cancer Research at MIT
Journal of Controlled Release
Ye, Hongye et al. “Sustained, Low-Dose Intraperitoneal Cisplatin Improves Treatment Outcome in Ovarian Cancer Mouse Models.” Journal of Controlled Release 220 (2015): 358–367.
Author's final manuscript