Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma

Karin Sorenmo, Marissa Samluk, Craig Clifford, Jennifer Baez, Jeffrey S. Barrett, Robert H Poppenga, Beth Overley, Katherine A Skorupski, Karen Oberthaler, Tom Van Winkle, Gabriela Seiler, Frances Shofer

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. Hypothesis: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. Animals: 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 IV delivery. Conclusions and Clinical Importance: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.

Original languageEnglish (US)
Pages (from-to)1347-1354
Number of pages8
JournalJournal of Veterinary Internal Medicine
Volume21
Issue number6
DOIs
StatePublished - Nov 2007

Fingerprint

hemangiosarcoma
Hemangiosarcoma
doxorubicin
pharmacokinetics
Pharmacokinetics
Dogs
dogs
Doxorubicin
Recurrence
metastasis
Autopsy
necropsy
liposomal doxorubicin
Neoplasm Metastasis
Neoplasms
neoplasms
Splenectomy
relapse
Abdomen
intraperitoneal injection

Keywords

  • Chemotherapy
  • Intraperitoneal administration
  • Pharmacokinetics
  • Splenic malignant endothelioma

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma. / Sorenmo, Karin; Samluk, Marissa; Clifford, Craig; Baez, Jennifer; Barrett, Jeffrey S.; Poppenga, Robert H; Overley, Beth; Skorupski, Katherine A; Oberthaler, Karen; Van Winkle, Tom; Seiler, Gabriela; Shofer, Frances.

In: Journal of Veterinary Internal Medicine, Vol. 21, No. 6, 11.2007, p. 1347-1354.

Research output: Contribution to journalArticle

Sorenmo, Karin ; Samluk, Marissa ; Clifford, Craig ; Baez, Jennifer ; Barrett, Jeffrey S. ; Poppenga, Robert H ; Overley, Beth ; Skorupski, Katherine A ; Oberthaler, Karen ; Van Winkle, Tom ; Seiler, Gabriela ; Shofer, Frances. / Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma. In: Journal of Veterinary Internal Medicine. 2007 ; Vol. 21, No. 6. pp. 1347-1354.
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T1 - Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma

AU - Sorenmo, Karin

AU - Samluk, Marissa

AU - Clifford, Craig

AU - Baez, Jennifer

AU - Barrett, Jeffrey S.

AU - Poppenga, Robert H

AU - Overley, Beth

AU - Skorupski, Katherine A

AU - Oberthaler, Karen

AU - Van Winkle, Tom

AU - Seiler, Gabriela

AU - Shofer, Frances

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N2 - 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. Hypothesis: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. Animals: 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 IV delivery. Conclusions and Clinical Importance: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.

AB - 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. Hypothesis: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. Animals: 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 IV delivery. Conclusions and Clinical Importance: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.

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