00841-A: Pharmacokinetics and Phase I Clinical Trial of High-Dose Intermittent Oral Artemisinin in Dogs with Spontaneous Tumors

Grant Amount: $12,904

Guillermo C. Couto, DVM; Ohio State University

October 1, 2006 - June 30, 2008

Sponsor(s):

Breed(s): -All Dogs

Research Program Area: Oncology

Abstract

Osteosarcoma is the most common primary bone cancer in dogs. The estimated incidence is 10,000 dogs per year in the United States. Many large- to giant-breeds are at increased risk for osteosarcoma. Recently, retired racing Greyhound have been reported as the highest-risk breed. Artemisinin is a drug that has been used anecdotally in dogs with osteosaroma. Originally, it was used for treatment of malaria in South Asia, but it also kills cancer cells due to free radical generation in a reaction mediated by iron. Cancer cells have higher iron concentration than normal cells, so artemisinin is selectively toxic. Artemisinin and its analogs are effective in several types of human cancer cells in test tubes. We have previously shown that low concentrations of artemisinin derivatives induce cell death in several types of canine cancer cells in the test tube. Artemisinin and its analogs have been used in clinical cancer treatment in people, and in dogs with osteosarcoma, with daily administration of small doses; however, there are few reports of successful outcome. A marked decrease of the gut absorption of artemisinin occurs within days if it is given daily. We hypothesize that high, pulse-dose artemisinin will be safe and effective in cancer treatment because it is unlikely to induce absorption resistance and it can achieve higher blood concentrations. This strategy has resulted in encouraging clinical responses in a limited number of dogs with cancer in our clinic. This study will investigate if the absorption resistance can be avoided by pulse-dosing of artemisinin, and the safety of high-dose artemisinin treatment in dogs. The data of this study are essential in order to design additional clinical trials for cancer therapy using this promising group of compounds.

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