Preclinical trial of doxorubicin entrapped in sterically stabilized liposomes in dogs with spontaneously arising malignant tumors

Cancer Chemother Pharmacol. 1997;39(5):410-6. doi: 10.1007/s002800050591.

Abstract

Purpose: 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.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antibiotics, Antineoplastic / toxicity
  • Dog Diseases*
  • Dogs
  • Doxorubicin / administration & dosage*
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Drug Carriers
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / veterinary
  • Liposomes
  • Male
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / veterinary*
  • Orchiectomy
  • Ovariectomy
  • Prospective Studies
  • Skin / drug effects
  • Skin / pathology

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Liposomes
  • Doxorubicin