Open AccessDoxorubicin and BAY 12–9566 for the Treatment of Osteosarcoma in Dogs: A Randomized, Double‐Blind, Placebo‐Controlled Study
Author(s) -
Moore Antony S.,
Dernell William S.,
Ogilvie Gregory K.,
Kristal Orna,
Elmslie Robyn,
Kitchell Barbara,
Susaneck Steven,
Rosenthal Robert,
Klein Mary K.,
Obradovoich Joyce,
Legendre Alfred,
Haddad Tara,
Hahn Kevin,
Powers Barbara E.,
Warren Darren
Publication year - 2007
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/j.1939-1676.2007.tb03022.x
Subject(s) - medicine , placebo , osteosarcoma , chemotherapy , amputation , doxorubicin , gastroenterology , surgery , urology , pathology , alternative medicine
Background : 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. Hypothesis : Survival will be prolonged in dogs receiving BAY 12–9566. Animals : The study included 303 dogs with appendicular osteosarcoma. Methods : Dogs were treated with doxorubicin (30 mg/m 2 ) 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. Results : 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. Conclusions and Clinical Importance : Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.