Preclinical trial of doxorubicin entrapped in sterically stabilized liposomes in dogs with spontaneously arising malignant tumors.
OBJECTIVE
To prospectively evaluate the short-term toxicoses associated with pegylated-liposomal doxorubicin (Doxil) administered to dogs with measurable tumors of various histologic types and sites. Preliminary information regarding efficacy was also generated.


METHODS
A group of 51 dogs with histologically confirmed malignancies received a total of 103 Doxil treatments given i.v. every 3 weeks at dosages ranging from 0.75 to 1.1 mg/kg in the context of a phase I dose-escalation trial. Acute and short-term toxicities as well as tumor response and duration of response were characterized.


RESULTS
The maximally tolerated dose in tumor-bearing dogs was established as 1.0 mg/kg i.v. every 3 weeks. The dose-limiting toxicity was a cutaneous toxicity clinically resembling palmar-plantar erythrodysesthesia (PPES). An overall response rate of 25.5% was observed with five complete responders and eight partial responders.


CONCLUSIONS
Doxil appeared to be well tolerated at dosages similar to those tolerated for free doxorubicin in tumor-bearing dogs. PPES was the dose-limiting toxicity encountered, rather than myelosuppresion as is the case with free doxorubicin in dogs. Doxil as a single agent may have a broad spectrum of activity and deserves further evaluation.
Vail
D M
DM
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706, USA. vaild@svm.vetmed.wisc.edu
Kravis
L D
LD
Cooley
A J
AJ
Chun
R
R
MacEwen
E G
EG
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D004283:Dog Diseases; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000662:veterinary; D008081:Liposomes; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D009919:Orchiectomy; D010052:Ovariectomy; D011446:Prospective Studies; D012867:Skin / Q000187:drug effects / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin