An Anticopper Antiangiogenic Approach for Advanced Cancer in Spontaneously Occurring Tumors Using Tetrathiomolybdate: A Pilot Study in a Canine Animal Model

Abstract

In this pilot study, 13 dogs of various breeds and ages with a variety of advanced tumors were treated with the antiangiogenic copper complexing drug tetrathiomolybdate. Dose escalations were performed to determine the safe and effective dose in dogs. The study was designed to last for a 6-month period for each dog entered. Dogs were examined weekly for the first 3 months and then every other week for the next 3 months. Complete blood count, serum biochemistry panel, and measurement of serum ceruloplasmin (Cp) content were conducted at each visit to monitor response to drug administration. Serum Cp was used as a surrogate marker of copper status. The owner reported toxicity at each visit. The dog was examined for physical abnormalities. Tumor measurements were completed every 2 weeks using direct measurements of the tumor with calipers in three planes or by direct measurements of the tumor using radiographic or ultrasonographic images in two planes. Tumor response was evaluated only after dogs achieved a 4-week reduction in their serum Cp content. Tumor responses were defined as either disease stabilization or reduction in tumor volume. Nine dogs achieved Cp reduction. Of those dogs, five had no response to treatment, whereas four dogs had tumor responses after Cp reduction, characterized as either disease stabilization or reduction in tumor volume, for the remainder of the study period. There was only mild self-limiting toxicity with use of the drug. © 2004 Wiley-Liss, Inc.