01192-A: Metabolism and Action of Gemcitabine in Canine Osteosarcoma Cell Lines

Grant Status: Closed

Grant Amount: $8,391.21
Dr. Carlos O. Rodriguez Jr, DVM PhD, University of California, Davis
September 1, 2008 - February 28, 2010
Sponsor(s): Border Collie Society of America, German Wirehaired Pointer Club of America, Staffordshire Bull Terrier Club of America
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

Osteosarcoma is the number one tumor of bone in both the dog. Despite surgery and chemotherapy, is only a 50% one year survival and the majority of osteosarcoma patients die from metastasis to their lungs. Therefore, there exists a need for the development of new well-tolerated treatments. Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC; Gemzar) is a drug that is not routinely used in frontline therapy of osteosarcoma. However, it has been shown to kill human osteosarcoma cell lines in tissue culture and in mice. Despite these studies in humans and mice, no studies utilizing cell lines derived from dogs have been reported. The purpose of this study is to determine how this drug works in canine osteosarcoma cell lines so that clinical trials using this drug in the fight against canine osteosarcoma can be performed optimally thus minimizing ineffective schedules or drug doses in dogs with bone cancer. The study is complete. Two major properties of gemcitabine in canine osteosarcoma, which may impact the way that this drug is used in pet dogs have been identified. The first is that gemcitabine is as effective against canine osteosarcoma as it has been shown for both human and mouse cell lines. An interesting and important second finding is that the drug is able to kill canine osteosarcoma at gemcitabine levels that are far lower than those that are obtained in serum when the drug is administered (in the conventional fashion) at the maximally tolerated dose as a 30-minute infusion. This finding suggests that reductions in total dose but increased time of exposure to the drug (through changes in administration such as 3-4 hour drips) may be a more effective application of the drug. Of course, clinical trials evaluating just this sort of change in protocol will be necessary to confirm or refute these in vitro findings in actual canine patients.

Publication(s)

Rodriguez, C.O., Crabbs, T.A., Wilson, D.W., Cannan V.C., Skorupski K.A., Gordon, N, Koshkina, N., Kleinerman, E.S. and Anderson, P.M. Aerosol gemcitabine: in vivo antitumor activity and preclinical safety assessment in osteosarcoma bearing dogs. J Aerosol Med Pulm Drug Deliv. 2009 Oct 5. [Epub ahead of print]. Manuscript entitled "The metabolism and action of gemcitabine in canine osteosarcoma" is being prepared.

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