• Open Access

An Open-Label, Dose-Escalating Phase I Study of Elsamitrucin (SPI 28090) in Treatment of Malignant Solid Tumors in Dogs


  • This work was performed at Veterinary Cancer Group, Tustin, CA 92780; Veterinary Cancer Group, Culver City, CA 90232; University of Missouri, Department of Veterinary Medicine and Surgery, Columbia, MO 65211.

Corresponding author: S. C. Fiocchi, DVM, Veterinary Cancer Group, 2887 Edinger Avenue, Tustin, CA 92627; e-mail: sfiocchi@vetcancergroup.com.


Background: Elsamitrucin, the most potent topoisomerase II inhibitor available, is unique in that it does not cause neutropenia or cardiotoxicosis. It has antitumor activity in human patients with relapsed or refractory non-Hodgkin's lymphoma.

Objectives: To determine the maximum tolerated dose (MTD), safety, and toxicity of elsamitrucin when administered to tumor-bearing dogs and to evaluate the incidence and severity of adverse events.

Animals: Twenty client-owned dogs with spontaneous malignant solid tumors or lymphoma that were refractory to, or for which the owner declined, conventional therapy were enrolled.

Methods: Prospective, open-label, single-agent study. Escalating doses of elsamitrucin were administered once weekly IV for up to 16 weeks in a modified 3 + 3 Phase I design. The starting dose was 0.06 mg/kg with escalation to 0.08 and 0.09 mg/kg. Dogs that remained on the study were monitored for evidence of toxicoses for at least 4 weeks and for survival every 2 months.

Results: Serious adverse events (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart failure and another developed hepatotoxicosis manifested by increased alanine aminotransferase, alkaline phosphatase, and total bilirubin (0.06 mg/kg dose); 1 dog developed severe anorexia and diarrhea, another developed severe diarrhea alone, and a 3rd dog went into cardiac arrest (0.09 mg/kg dose). A dose of 0.08 mg/kg was well tolerated with no SAEs.

Conclusions and Clinical Importance: The MTD and recommended dose for Phase II trials of elsamitrucin is 0.08 mg/kg IV weekly. Elsamitrucin might be considered for combination protocols with myelosuppressive chemotherapy agents.