Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma.
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.
Sorenmo
Karin
K
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
Samluk
Marissa
M
Clifford
Craig
C
Baez
Jennifer
J
Barrett
Jeffrey S
JS
Poppenga
Robert
R
Overley
Beth
B
Skorupski
Katherine
K
Oberthaler
Karen
K
Van Winkle
Tom
T
Seiler
Gabriela
G
Shofer
Frances
F
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*
D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin