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This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. Survival will be prolonged in dogs receiving BAY 12-9566. The study included 303 dogs with appendicular osteosarcoma. Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.


Antony S Moore, William S Dernell, Gregory K Ogilvie, Orna Kristal, Robyn Elmslie, Barbara Kitchell, Steven Susaneck, Robert Rosenthal, Mary K Klein, Joyce Obradovich, Alfred Legendre, Tara Haddad, Kevin Hahn, Barbara E Powers, Darren Warren. Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine. 2007 Jul-Aug;21(4):783-90

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PMID: 17708400

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