title: 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/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.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Hongye
authors.initials: H
authors.lastname: Ye
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tanenbaum
authors.affiliation: Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Young Jeong
authors.initials: YJ
authors.lastname: Na
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Mantzavinou
authors.affiliation: Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fulci
authors.affiliation: Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Marcela G
authors.initials: MG
authors.lastname: Del Carmen
authors.affiliation: Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: mjcima@mit.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004339:Drug Compounding; D004343:Drug Implants; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008819:Mice, Nude; D008904:Miniaturization; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012995:Solubility; D047368:Tumor Burden / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004343:Drug Implants; D002945:Cisplatin
keywords: Cisplatin; Cisplatinum (PubChem CID: 441203); Continuous; Drug delivery; Intraperitoneal; Ovarian cancer