Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study.
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.


OBJECTIVE
Survival will be prolonged in dogs receiving BAY 12-9566.


METHODS
The study included 303 dogs with appendicular osteosarcoma.


METHODS
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.


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
Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.
Moore
Antony S
AS
Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. voc@vetoncologyconsults.com
Dernell
William S
WS
Ogilvie
Gregory K
GK
Kristal
Orna
O
Elmslie
Robyn
R
Kitchell
Barbara
B
Susaneck
Steven
S
Rosenthal
Robert
R
Klein
Mary K
MK
Obradovich
Joyce
J
Legendre
Alfred
A
Haddad
Tara
T
Hahn
Kevin
K
Powers
Barbara E
BE
Warren
Darren
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D009202:Cardiomyopathies / Q000139:chemically induced / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D009930:Organic Chemicals / Q000008:administration & dosage* / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy / Q000662:veterinary*; D010654:Phenylbutyrates
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D009930:Organic Chemicals; D010654:Phenylbutyrates; D004317:Doxorubicin; C113281:Bay 12-9566