title: Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma.
abstract: BACKGROUND
  Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence.
  
  
  OBJECTIVE
  Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA.
  
  
  METHODS
  Fourteen dogs with splenic HSA.
  
  
  METHODS
  A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP.
  
  
  RESULTS
  All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery.
  
  
  CONCLUSIONS
  IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.
authors.affiliation: School of Veterinary Medicine, Department of Clinical Studies, MJ Ryan Veterinary Hospital of the University of Pennsylvania, 3900 Delancy Street, Philadelphia, PA 19104, USA. karins@vet.upenn.edu
authors.forename: Karin
authors.initials: K
authors.lastname: Sorenmo
authors.forename: Marissa
authors.initials: M
authors.lastname: Samluk
authors.forename: Craig
authors.initials: C
authors.lastname: Clifford
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baez
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Robert
authors.initials: R
authors.lastname: Poppenga
authors.forename: Beth
authors.initials: B
authors.lastname: Overley
authors.forename: Katherine
authors.initials: K
authors.lastname: Skorupski
authors.forename: Karen
authors.initials: K
authors.lastname: Oberthaler
authors.forename: Tom
authors.initials: T
authors.lastname: Van Winkle
authors.forename: Gabriela
authors.initials: G
authors.lastname: Seiler
authors.forename: Frances
authors.initials: F
authors.lastname: Shofer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000662:veterinary*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013160:Splenic Neoplasms / Q000188:drug therapy / Q000662:veterinary*
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin